subject:(somatic mutations)

University of Cambridge

1. GARG, SUMEDHA. Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal.

Degree: PhD, 2019, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/289390

► Primary aldosteronism (PA) accounts for 5-10% of all hypertension. One of the major causes of PA is sporadic formation of aldosterone-producing adenomas (APAs). These benign… (more)

▼ Primary aldosteronism (PA) accounts for 5-10% of all hypertension. One of the major causes of PA is sporadic formation of aldosterone-producing adenomas (APAs). These benign tumours develop in the cortical region of adrenal glands and autonomously secrete excessive amounts of aldosterone. This hormone increases sodium retention and water reabsorption by the kidneys, leading to high blood pressure. Landmark discoveries of somatic mutations in APAs led to better understanding of molecular mechanisms causing autonomous aldosterone secretion. The first mutations were found in KCNJ5, followed by ATP1A1, ATP2B3 and CACNA1D, all encoding cation-channels or transporters. Several in vitro studies showed disruption of cellular ion-balance leading to the phenotype of hyper-aldosterone secretion from APAs. Following our lab’s discovery of initial four somatic mutations by whole exome sequencing, over 30 single-base change mutations have been reported in the CACNA1D gene, which encodes the a1 subunit of an L-type Ca2+ channel (LTCC), CaV1.3. Initial and several subsequent mutations cause electrophysiological gain-of-function with increased activation and/or slowed inactivation of CaV1.3. Prior to the discovery of these mutations, L-type Ca2+ channels were not considered important in regulation of aldosterone production. In the first part of my thesis, I investigated two of the mutations and showed that the gain-of-function results in increased aldosterone secretion from an adrenocortical carcinoma cell line, H295R, when transiently transfected with the mutants. I also showed that CaV1.3 can play a role in physiological aldosterone secretion, finding that CYP11B2 expression is reduced by 50% in the adrenals of CaV1.3 knockout mice. The discovery of mutations in CACNA1D led to a drug discovery challenge award from a pharmaceutical company in which high-throughput screening of CaV1.3-expressing cells was undertaken against the company's 1.8M compound library. I identified the adrenal isoforms of the channel's alpha and beta subunits (CACNA1D and CACNB2), and helped development of the stable HEK293 cell line used for screening. This led to 3 tool compounds (A, B & C) that were selective antagonists for CaV1.3 over another family member of the ion channels in high-throughput electrophysiological experiments using IonWorks Barracuda and QPatch platforms. I showed compound B to effectively inhibit aldosterone secretion in both H295R and primary adrenal cells isolated from a normal adrenal. This finding is a significant step in developing compound B further into a CaV1.3-selective drug for treating PA patients without cardiovascular side effects as in the case of existing dihydropyridine class of Ca2+ channel blockers. The second part of my thesis focused on genotyping and whole exome sequencing of 59 APAs from 52 patients, in order to identify further genes underlying primary aldosteronism. Mutations in previously reported genes were identified in 34 of the APAs (57.6%). CACNA1D was the most commonly mutated gene (20.3%) in this…

Subjects/Keywords: aldosterone; adenoma; somatic mutations; hypertension

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APA (6^th Edition):

GARG, S. (2019). Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/289390

Chicago Manual of Style (16^th Edition):

GARG, SUMEDHA. “Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 22, 2021. https://www.repository.cam.ac.uk/handle/1810/289390.

MLA Handbook (7^th Edition):

GARG, SUMEDHA. “Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal.” 2019. Web. 22 Jan 2021.

Vancouver:

GARG S. Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 22]. Available from: https://www.repository.cam.ac.uk/handle/1810/289390.

Council of Science Editors:

GARG S. Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/289390

University of California – Santa Cruz

2. Radenbaugh, Amie. The Identification and Characterization of Alterations to DNA and RNA in Cancer Using Next-Generation Sequencing Data.

Degree: Biomolecular Engineering and Bioinformatics, 2015, University of California – Santa Cruz

URL: http://www.escholarship.org/uc/item/0dt1w1fx

► Much of our current understanding of cancer has come from investigating how normal cells are transformed into malignant cancers through the stepwise acquisition of somatic… (more)

▼ Much of our current understanding of cancer has come from investigating how normal cells are transformed into malignant cancers through the stepwise acquisition of somatic genomic abnormalities. These abnormalities include single nucleotide variants (SNVs), insertions and deletions (INDELs), chromosomal rearrangements, and copy number aberrations. The detection of SNVs is a crucial component to the characterization of the cancer genome. They assist in identifying key genes as possible drug targets, diagnostic markers for early detection, and prognostic markers for monitoring a patient's response to therapy. Variant calling algorithms thus far have focused on comparing the normal and tumor genomes from the same individual. In recent years, it has become routine for projects like The Cancer Genome Atlas (TCGA) to also sequence the tumor RNA. A novel computational method called RADIA (RNA and DNA Integrated Analysis) that combines the patient-matched normal and tumor DNA with the tumor RNA to detect SNVs is presented here. RADIA has detected somatic mutations for nearly 4,500 patients across 22 different cancers, and including the RNA provided a 2-7% increase in sensitivity.RNA editing is an additional epigenetic mechanism involved in cancer development and progression. RNA editing of the AZIN1 gene has been identified as a driver in the pathogenesis of hepatocellular carcinoma and may be a potential driver for other human cancers as well. An investigation of AZIN1 RNA editing in data collected from nearly 5,000 patients across 12 cancers has been performed. Higher editing frequencies significantly correlated with clinical data such as larger tumor sizes, greater lymph node involvement, the presence of metastases, and higher tumor grades. They were also associated with subtypes that often have the worst prognosis. Over-editing in many cancers is correlated with poor overall and recurrence free survival. With projects like TCGA providing sequencing data for both DNA and RNA from the same patients across multiple cancers, it is now possible to characterize germline variants, somatic mutations, and RNA editing events on a genome-wide scale. The identification of SNVs that occur in specific genes across multiple cancers provides a powerful way to discover genes that are important to these diseases.

Subjects/Keywords: Bioinformatics; editing; mutations; NGS; RNA; somatic; variants

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APA (6^th Edition):

Radenbaugh, A. (2015). The Identification and Characterization of Alterations to DNA and RNA in Cancer Using Next-Generation Sequencing Data. (Thesis). University of California – Santa Cruz. Retrieved from http://www.escholarship.org/uc/item/0dt1w1fx

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Radenbaugh, Amie. “The Identification and Characterization of Alterations to DNA and RNA in Cancer Using Next-Generation Sequencing Data.” 2015. Thesis, University of California – Santa Cruz. Accessed January 22, 2021. http://www.escholarship.org/uc/item/0dt1w1fx.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Radenbaugh, Amie. “The Identification and Characterization of Alterations to DNA and RNA in Cancer Using Next-Generation Sequencing Data.” 2015. Web. 22 Jan 2021.

Vancouver:

Radenbaugh A. The Identification and Characterization of Alterations to DNA and RNA in Cancer Using Next-Generation Sequencing Data. [Internet] [Thesis]. University of California – Santa Cruz; 2015. [cited 2021 Jan 22]. Available from: http://www.escholarship.org/uc/item/0dt1w1fx.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Radenbaugh A. The Identification and Characterization of Alterations to DNA and RNA in Cancer Using Next-Generation Sequencing Data. [Thesis]. University of California – Santa Cruz; 2015. Available from: http://www.escholarship.org/uc/item/0dt1w1fx

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Maddaly Ravi. Analysis of somatic cell mutations at the Glycophorina locus in human erythrocytes.

Degree: Human Genetics, 2001, Sri Ramachandra University

URL: http://shodhganga.inflibnet.ac.in/handle/10603/17910

►

Introduction: Dose evaluation of exposed humans to radiation becomes necessary after exposure. Such a dose evaluation can be done by biological dosimetric methods of which… (more)

▼

Introduction: Dose evaluation of exposed humans to radiation becomes necessary after exposure. Such a dose evaluation can be done by biological dosimetric methods of which increased somatic cell mutant frequencies in exposed individuals can be a reliable index [1]. Biological dosimetry has an important role to play in assessing the cumulative radiation exposure of persons working with radiation and also in estimating the true dose received during accidents involving external and internal exposure. Biodosimetric methods include cytogenetic, immunological and mutational assays [2]. The need for biodosimetry is essential for caliberating the actual dose received to a biological system where other conventional forms of dosimetry are unavailable. Even in the presence of other dosimetric tools such as Thermo Luminescent Devices (TLDs) etc, biological dosimetry gives actual doses apart from an indication of the extent of damage caused by such damages. This becomes all the more important with the current situations such as space programmes and dirty bombs. There are currently many advancing methods for measuring somatic mutations and new opportunities for biological dosimetry of high-risk groups. An evaluation of such mutations becomes all the more important, as such mutations can be possible predictors of cancer risk [3]. Somatic mutations can now be measured in several human genes. The genes currently used include the hemoglobin (Hb) genes on chromosome 11 and 16, the glycophorin A (GPA) gene on chromosome 4, the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene on the Xchromosome, the HLA genes on the chromosome 6 and the T-cell receptor (TCR) genes on chromosomes 7 and 14. Of the various assays for somatic mutations, only GPA and HPRT have been studied sufficiently to have reliable databases. With increasing interest in the GPA mutation assay for biodosimetry and assessment of health risks, the techniques used to detect the variant cells have been undergoing constant changes and evolution from 1986

Reference included

Advisors/Committee Members: Paul, Solomon F D.

Subjects/Keywords: Glycophorina; Human erythrocytes; Somatic cell mutations

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APA (6^th Edition):

Ravi, M. (2001). Analysis of somatic cell mutations at the Glycophorina locus in human erythrocytes. (Thesis). Sri Ramachandra University. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/17910

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ravi, Maddaly. “Analysis of somatic cell mutations at the Glycophorina locus in human erythrocytes.” 2001. Thesis, Sri Ramachandra University. Accessed January 22, 2021. http://shodhganga.inflibnet.ac.in/handle/10603/17910.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ravi, Maddaly. “Analysis of somatic cell mutations at the Glycophorina locus in human erythrocytes.” 2001. Web. 22 Jan 2021.

Vancouver:

Ravi M. Analysis of somatic cell mutations at the Glycophorina locus in human erythrocytes. [Internet] [Thesis]. Sri Ramachandra University; 2001. [cited 2021 Jan 22]. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/17910.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ravi M. Analysis of somatic cell mutations at the Glycophorina locus in human erythrocytes. [Thesis]. Sri Ramachandra University; 2001. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/17910

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign

4. Zhang, Yang. Computational approaches for analyzing regulatory regions in the human genome.

Degree: PhD, Bioengineering, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/99491

► The cis-regulatory elements (CRE) in the human genome play a critical role in transcriptional regulation. Alterations of the CRE have long been considered as the… (more)

▼ The cis-regulatory elements (CRE) in the human genome play a critical role in transcriptional regulation. Alterations of the CRE have long been considered as the driving force of the human evolution. Recent studies also suggest that somatic mutations within the CRE can act as driver factors in cancer. With the growth of the quantity and the variety of genomic data, more biological functions of CRE remain to be determined. However, the bottleneck of analyzing the human CRE lies in the lack of the holistic approaches to integrating multi-dimensional genomic data and exploring their roles in human biology. The primary motivation of this dissertation is to provide novel insights of the human CRE by developing integrative computational approaches to consolidating versatile genomic data. Specifically, we developed three computational algorithms/frameworks to decipher the complex functions of the human CRE: 1) in the evolutionary context of comparative genomics, 2) in the context of cancer somatic mutations, and 3) in the context of 3D chromatin organization. In the first part of this dissertation, we explored the functions of the lineage-specific TFBS in the human genome using ANTICE, a novel probabilistic algorithm developed by us. Compared to previous methods, ANTICE is favored for its ability to predict lineage-specific TFBS under a phylogenetic model and also account for the uncertainty of the multiple sequence alignment (MSA) and high turnover rate of TFBS. Based on ANTICE, we generated by far the largest genome-wide landscape of lineage-specific transcription factor binding sites (TFBS) using 680 human ChIP-seq datasets from the ENCODE project. We then integrated lineage-specific human TFBS with public genomic data. We discovered that a substantial fraction of human TFBS has emerged after the human-mouse divergence. Younger TFBS, compared to the ancestral TFBS conserved between human and mouse, tend to locate further away from the gene promoters, more likely to involve in the tissue-specific open chromatin regions, and are enriched for common SNP and germline mutations. Our study provides the first genome-wide resources of the locations of lineage-specific TFBS in the human genome, which can help to explain how human become human in the course of the evolution. In the second part of this dissertation, we developed an integrated analysis framework to explore how the genomic context of the CRE influence the UV induced mutagenesis at CRE in Melanoma patients. We discovered that mutation rate of C to T mutations at tumor-specific DNase I hypersensitive site (DHS) are significantly associated with the genomic features of DHS represented by the distance of DHS to the TSS, DNA sequence composition of DHS and the H3K4me3 signal of DHS. We also found that these genomic features often jointly determine the landscape of the mutation rate at DHS. Within DHS regions, somatic mutations are enriched at binding sites with CGGAAT or CTCF motifs, which suggests a potential positive selection phenomenon at CRE in Melanoma.… Advisors/Committee Members: Ma, Jian (advisor), Ma, Jian (Committee Chair), Belmont, Andrew (committee member), Stubbs, Lisa (committee member), Sinha, Saurabh (committee member), Warnow, Tandy (committee member).

Subjects/Keywords: Regulatory elements; Evolution; Somatic mutations; Chromatin organization

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, Y. (2017). Computational approaches for analyzing regulatory regions in the human genome. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/99491

Chicago Manual of Style (16^th Edition):

Zhang, Yang. “Computational approaches for analyzing regulatory regions in the human genome.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 22, 2021. http://hdl.handle.net/2142/99491.

MLA Handbook (7^th Edition):

Zhang, Yang. “Computational approaches for analyzing regulatory regions in the human genome.” 2017. Web. 22 Jan 2021.

Vancouver:

Zhang Y. Computational approaches for analyzing regulatory regions in the human genome. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2142/99491.

Council of Science Editors:

Zhang Y. Computational approaches for analyzing regulatory regions in the human genome. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/99491

UCLA

5. Chang, Vivian Y. Whole Exome Sequencing of Pediatric Gastric Adenocarcinoma: A Germline and Somatic Mutation Analysis.

Degree: Bioinformatics, 2012, UCLA

URL: http://www.escholarship.org/uc/item/5bg855cr

► BackgroundGastric adenocarcinoma is a rare diagnosis in childhood. A 14-year old male patient presented with metastatic gastric adenocarcinoma, and a strong family history of colon… (more)

Subjects/Keywords: Molecular biology; Bioinformatics; Genetics; exome sequencing; germline mutations; pediatric cancer; somatic mutations

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chang, V. Y. (2012). Whole Exome Sequencing of Pediatric Gastric Adenocarcinoma: A Germline and Somatic Mutation Analysis. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/5bg855cr

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chang, Vivian Y. “Whole Exome Sequencing of Pediatric Gastric Adenocarcinoma: A Germline and Somatic Mutation Analysis.” 2012. Thesis, UCLA. Accessed January 22, 2021. http://www.escholarship.org/uc/item/5bg855cr.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chang, Vivian Y. “Whole Exome Sequencing of Pediatric Gastric Adenocarcinoma: A Germline and Somatic Mutation Analysis.” 2012. Web. 22 Jan 2021.

Vancouver:

Chang VY. Whole Exome Sequencing of Pediatric Gastric Adenocarcinoma: A Germline and Somatic Mutation Analysis. [Internet] [Thesis]. UCLA; 2012. [cited 2021 Jan 22]. Available from: http://www.escholarship.org/uc/item/5bg855cr.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chang VY. Whole Exome Sequencing of Pediatric Gastric Adenocarcinoma: A Germline and Somatic Mutation Analysis. [Thesis]. UCLA; 2012. Available from: http://www.escholarship.org/uc/item/5bg855cr

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. G.E.M. Melloni. COMPUTATIONAL FRAMEWORKS FOR THE IDENTIFICATION OF SOMATIC AND GERMLINE VARIANTS CONTRIBUTING TO CANCER PREDISPOSITION AND DEVELOPMENT.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/462986

► The most recent cancer classification from NIH includes ~200 types of tumor that originates from several tissue types (http://www.cancer.gov/types). Although macroscopic and microscopic characteristics varies… (more)

▼ The most recent cancer classification from NIH includes ~200 types of tumor that originates from several tissue types (http://www.cancer.gov/types). Although macroscopic and microscopic characteristics varies significantly across subtypes, the starting point of every cancer is believed to be a single cell that acquires DNA somatic alterations that increases its fitness over the surrounding cells and makes it behave abnormally and proliferate uncontrollably. Somatic mutations are the consequence of many possible defective processes such as replication deficiencies, exposure to carcinogens, or DNA repair machinery faults. Mutation development is a random and mostly natural process that frequently happens in every cell of an individual. Only the acquisition of a series of subtype-specific alterations, including also larger aberrations such as translocations or deletions, can lead to the development of the disease and this is a long process for the majority of adult tumor types. However, genetic predisposition for certain cancer types is epidemiologically well established. In fact, several cancer predisposing genes where identified in the last 30 years with various technologies but they characterize only a small fraction of familial cases. This work will therefore cover two main steps of cancer genetics and genomics: the identification of the genes that somatically changes the behavior of a normal human cell to a cancer cell and the genetic variants that increase risk of cancer development. The use of publicly available datasets is common to all the three results sections that compose this work. In particular, we took advantage of several whole exome sequencing databases (WES) for the identification of both driver mutations and driver variants. In particular, the use of WES in cancer predisposition analysis represents one of the few attempts of performing such analysis on genome-wide sequencing germline data. Advisors/Committee Members: supervisor: Pelicci Pier Giuseppe, co-supervisor: Riva, Laura, internal advisor: Bagnardi, Vincenzo, external advisor: Markowetz, Florian, PELICCI, PIER GIUSEPPE.

Subjects/Keywords: Somatic Mutations; Germline Mutations; Next Generation Sequencing; Whole Exome Sequencing; Settore MED/04 - Patologia Generale

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APA (6^th Edition):

Melloni, G. (2017). COMPUTATIONAL FRAMEWORKS FOR THE IDENTIFICATION OF SOMATIC AND GERMLINE VARIANTS CONTRIBUTING TO CANCER PREDISPOSITION AND DEVELOPMENT. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/462986

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Melloni, G.E.M.. “COMPUTATIONAL FRAMEWORKS FOR THE IDENTIFICATION OF SOMATIC AND GERMLINE VARIANTS CONTRIBUTING TO CANCER PREDISPOSITION AND DEVELOPMENT.” 2017. Thesis, Università degli Studi di Milano. Accessed January 22, 2021. http://hdl.handle.net/2434/462986.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Melloni, G.E.M.. “COMPUTATIONAL FRAMEWORKS FOR THE IDENTIFICATION OF SOMATIC AND GERMLINE VARIANTS CONTRIBUTING TO CANCER PREDISPOSITION AND DEVELOPMENT.” 2017. Web. 22 Jan 2021.

Vancouver:

Melloni G. COMPUTATIONAL FRAMEWORKS FOR THE IDENTIFICATION OF SOMATIC AND GERMLINE VARIANTS CONTRIBUTING TO CANCER PREDISPOSITION AND DEVELOPMENT. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2434/462986.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Melloni G. COMPUTATIONAL FRAMEWORKS FOR THE IDENTIFICATION OF SOMATIC AND GERMLINE VARIANTS CONTRIBUTING TO CANCER PREDISPOSITION AND DEVELOPMENT. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/462986

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University

7. Song, Zhuo. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.

Degree: PhD, Human Genetics, 2012, Vanderbilt University

URL: http://hdl.handle.net/1803/10702

► The activity of polymerase ã (pol ã) is complicated. To understand how its kinetics values affect the final function of the pol ã, I created… (more)

Subjects/Keywords: tumor somatic mutations; targeted sequencing; NRTI; polymerase gamma; mtDNA replication

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Song, Z. (2012). Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10702

Chicago Manual of Style (16^th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/10702.

MLA Handbook (7^th Edition):

Song, Zhuo. “Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data.” 2012. Web. 22 Jan 2021.

Vancouver:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/10702.

Council of Science Editors:

Song Z. Stochastic modeling of mitochondrial polymerase gamma replication and novel algorithms to enrich rare disease alleles and detect tumor somatic mutations in deep sequencing data. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/10702

Delft University of Technology

8. Dentro, S.C. (author). Interpretable classification of tumours through multiple instance learning and somatic mutations.

Degree: 2013, Delft University of Technology

URL: http://resolver.tudelft.nl/uuid:e23175cb-d1a8-4cb6-af7b-9909f6412cf5

►

Next generation sequencing is brought into the clinic. Screening of disease associated genes will aid the diagnosis of disorders with a genetic component. The diagnosis… (more)

Subjects/Keywords: cancer; multiple instance learning; somatic mutations; classification; machine learning

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APA (6^th Edition):

Dentro, S. C. (. (2013). Interpretable classification of tumours through multiple instance learning and somatic mutations. (Masters Thesis). Delft University of Technology. Retrieved from http://resolver.tudelft.nl/uuid:e23175cb-d1a8-4cb6-af7b-9909f6412cf5

Chicago Manual of Style (16^th Edition):

Dentro, S C (author). “Interpretable classification of tumours through multiple instance learning and somatic mutations.” 2013. Masters Thesis, Delft University of Technology. Accessed January 22, 2021. http://resolver.tudelft.nl/uuid:e23175cb-d1a8-4cb6-af7b-9909f6412cf5.

MLA Handbook (7^th Edition):

Dentro, S C (author). “Interpretable classification of tumours through multiple instance learning and somatic mutations.” 2013. Web. 22 Jan 2021.

Vancouver:

Dentro SC(. Interpretable classification of tumours through multiple instance learning and somatic mutations. [Internet] [Masters thesis]. Delft University of Technology; 2013. [cited 2021 Jan 22]. Available from: http://resolver.tudelft.nl/uuid:e23175cb-d1a8-4cb6-af7b-9909f6412cf5.

Council of Science Editors:

Dentro SC(. Interpretable classification of tumours through multiple instance learning and somatic mutations. [Masters Thesis]. Delft University of Technology; 2013. Available from: http://resolver.tudelft.nl/uuid:e23175cb-d1a8-4cb6-af7b-9909f6412cf5

University of Edinburgh

9. Pethick, Joanna Margaret. Detecting selection in the evolution of cancer genomes.

Degree: PhD, 2015, University of Edinburgh

URL: http://hdl.handle.net/1842/19548

► Cancer is a disease of the genome, requiring mutation or epimutation of specific genes to develop. The subsequent progression of cancer and response to therapies… (more)

▼ Cancer is a disease of the genome, requiring mutation or epimutation of specific genes to develop. The subsequent progression of cancer and response to therapies is also dictated to some degree by new mutation and clonal selection on that novel variation. However, it is thought that the majority of somatic mutations that occur in cancer are inconsequential passengers, and only a subset of functionally important driver mutations are of importance for cancer biology. This project set out to adapt and apply well-established methods from the field of molecular evolution to measure the selective forces driving the development of cancers. The ultimate objective being an improved understanding of which mutations help or hinder the progression of a cancer. Somatic cancer mutations were identified through the analysis of paired tumour and non-tumour whole-exome sequence data from the same individual. Primary data from 1005 patients was processed and complemented with additional publicly available pre-processed somatic variant calls from 4728 patients. Tumours were classified by tissue of origin and also their spectrum of substitution mutations. An advanced evolutionary analysis framework was established, allowing somatic single nucleotide variant data to be analysed as traditional organismal DNA sequence. Estimates of amino acid changing (non-synonymous) and synonymous mutation rates were derived and maximum likelihood tests of selection applied to identify genes and regions of genes subject to selective pressure during oncogenesis. While the meta-analysis of all patients provided unprecedented power for such a study, more refined analyses based on the stratification of patients gave insights into the pathways of importance for specific tissues of origin. Additionally, stratification of patients by the relative frequencies of different mutation types in a tumour also provided insights into how mutation profile influences the sites, genes and pathways that are perturbed in the development of cancer. Of particular interest here, was to test the hypothesis that both (1.) mutation spectrum and (2.) tissue of origin, set the evolutionary trajectory of a cancer. Building on this I sought to estimate their relative contributions. During this work an unexpected, localised mutation pattern was discovered and subsequent analysis demonstrated some loci to be highly susceptible to small segmental deletions in a subset of cancers. In the absence of a justifiable model of neutral segmental deletion it was not possible to infer whether these major mutations could be considered passengers or drivers of cancer progression. In contrast, an advantage of the evolutionary approach applied to nucleotide substitutions in protein coding sequences is that there is a justified model of neutral evolution (synonymous changes). Using this approach, I have not only been able to detect genes harbouring putative cancer driver mutations, but have also found evidence for genes subject to purifying selection in cancers where potentially disruptive mutations…

Subjects/Keywords: 616.99; somatic cancer mutations; advanced evolutionary analysis framework; localised mutation pattern

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APA (6^th Edition):

Pethick, J. M. (2015). Detecting selection in the evolution of cancer genomes. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/19548

Chicago Manual of Style (16^th Edition):

Pethick, Joanna Margaret. “Detecting selection in the evolution of cancer genomes.” 2015. Doctoral Dissertation, University of Edinburgh. Accessed January 22, 2021. http://hdl.handle.net/1842/19548.

MLA Handbook (7^th Edition):

Pethick, Joanna Margaret. “Detecting selection in the evolution of cancer genomes.” 2015. Web. 22 Jan 2021.

Vancouver:

Pethick JM. Detecting selection in the evolution of cancer genomes. [Internet] [Doctoral dissertation]. University of Edinburgh; 2015. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1842/19548.

Council of Science Editors:

Pethick JM. Detecting selection in the evolution of cancer genomes. [Doctoral Dissertation]. University of Edinburgh; 2015. Available from: http://hdl.handle.net/1842/19548

Vanderbilt University

10. O'Brien, Timothy Daniel. Investigating the Genetic Influences of the Germline and Somatic Genomes in Three Subtypes of Lung Cancer.

Degree: PhD, Human Genetics, 2017, Vanderbilt University

URL: http://hdl.handle.net/1803/12384

► Lung cancer is classified into two main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC has several subtypes, but the… (more)

▼ Lung cancer is classified into two main types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC has several subtypes, but the two most commonly occurring subtypes are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). These classifications are mostly based upon histological and pathological characteristics, but there is increasing evidence of genetic and molecular differences as well. Although previous work has identified differences between subtypes of NSCLC at the somatic level, little work has been done to look at differences in all three subtypes across both the germline and somatic genomes. I hypothesized that a comprehensive detailed comparison of these lung cancer subtypes at both genomes would reveal shared and distinct mechanisms of disease. In this work, I used single nucleotide polymorphisms (SNPs) identified as significant (p < 1 x 10-3) in a genome wide association study (GWAS) to identify regulatory variants associated with each lung cancer subtype. I used these regulatory SNPs to identify sets of regulated genes in the genome for each subtype. I also expanded this germline work across other lung diseases and cancer types to extend the utility of the pipeline. At the somatic level, I identified genes that were differentially expressed in lung tumor versus normal tissue. Additionally, I identified mutational signatures and sets of potential driver genes in the somatic genomes for each subtype. I also identified biological pathways enriched with the germline and somatic gene sets. Finally, I performed a detailed comparison of calling somatic single nucleotide variants (SNVs) from whole exome sequencing (WES) versus transcriptome sequencing (RNA-Seq) in NSCLC. Overall, across all comparisons and genomes, I observed very little overlap between the three lung cancer subtypes. However, I found one gene, CHRNA5, disrupted by regulatory variants in the germline genomes and differentially expressed in the somatic genomes. This gene encodes a nicotinic acetylcholine receptor and may play a role in lung cancer due to its finding across both genomes and all three subtypes. Advisors/Committee Members: John A. Capra (committee member), Melinda Aldrich (committee member), Jirong Long (committee member), Nancy Cox (committee member), Zhongming Zhao (committee member), David Samuels (Committee Chair).

Subjects/Keywords: RNA-Seq; WES; somatic mutations; differential expression; enhancer; eQTL; lung cancer subtypes; GWAS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

O'Brien, T. D. (2017). Investigating the Genetic Influences of the Germline and Somatic Genomes in Three Subtypes of Lung Cancer. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12384

Chicago Manual of Style (16^th Edition):

O'Brien, Timothy Daniel. “Investigating the Genetic Influences of the Germline and Somatic Genomes in Three Subtypes of Lung Cancer.” 2017. Doctoral Dissertation, Vanderbilt University. Accessed January 22, 2021. http://hdl.handle.net/1803/12384.

MLA Handbook (7^th Edition):

O'Brien, Timothy Daniel. “Investigating the Genetic Influences of the Germline and Somatic Genomes in Three Subtypes of Lung Cancer.” 2017. Web. 22 Jan 2021.

Vancouver:

O'Brien TD. Investigating the Genetic Influences of the Germline and Somatic Genomes in Three Subtypes of Lung Cancer. [Internet] [Doctoral dissertation]. Vanderbilt University; 2017. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1803/12384.

Council of Science Editors:

O'Brien TD. Investigating the Genetic Influences of the Germline and Somatic Genomes in Three Subtypes of Lung Cancer. [Doctoral Dissertation]. Vanderbilt University; 2017. Available from: http://hdl.handle.net/1803/12384

University of Toronto

11. Green, Blerta. The Mismatch Repair Pathway Functions Normally at a non-AID Target in Germinal Center B cells.

Degree: 2011, University of Toronto

URL: http://hdl.handle.net/1807/30614

►

Deficiency in Msh2, a component of the mismatch repair (MMR) system, leads to a ~10-fold increase in the mutation frequency in most tissues. By contrast,… (more)

Subjects/Keywords: mismatch repair; somatic hypermutation; germinal center; activation induced cytidine deaminase; B cells; mutations; 0982

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Green, B. (2011). The Mismatch Repair Pathway Functions Normally at a non-AID Target in Germinal Center B cells. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/30614

Chicago Manual of Style (16^th Edition):

Green, Blerta. “The Mismatch Repair Pathway Functions Normally at a non-AID Target in Germinal Center B cells.” 2011. Masters Thesis, University of Toronto. Accessed January 22, 2021. http://hdl.handle.net/1807/30614.

MLA Handbook (7^th Edition):

Green, Blerta. “The Mismatch Repair Pathway Functions Normally at a non-AID Target in Germinal Center B cells.” 2011. Web. 22 Jan 2021.

Vancouver:

Green B. The Mismatch Repair Pathway Functions Normally at a non-AID Target in Germinal Center B cells. [Internet] [Masters thesis]. University of Toronto; 2011. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1807/30614.

Council of Science Editors:

Green B. The Mismatch Repair Pathway Functions Normally at a non-AID Target in Germinal Center B cells. [Masters Thesis]. University of Toronto; 2011. Available from: http://hdl.handle.net/1807/30614

Rice University

12. Chen, Zhongyuan. Association Studies in Human Cancers: Metabolic Expression Subtypes and Somatic Mutations/Germline Variations.

Degree: PhD, Engineering, 2019, Rice University

URL: http://hdl.handle.net/1911/106172

► Cancer is a highly complex genetic disease caused by certain gene mutations. This thesis focuses on two critical categories of association studies for human cancers:… (more)

▼ Cancer is a highly complex genetic disease caused by certain gene mutations. This thesis focuses on two critical categories of association studies for human cancers: associations between tumor metabolic subtypes and various other cancer aspects, and associations between somatic mutations and germline variations. In the first category, we classify metabolic expression subtypes in multiple TCGA (the Cancer Genome Atlas) cancer types, identify consistent prognostic patterns, and analyze master regulators of metabolic subtypes. We apply various statistical methods to study the associations between the metabolic expression subtypes and patients' survival, somatic mutations, copy number variations, and hallmark pathways. The results show that the metabolic expression subtypes are extensively correlated with patients' survival. The work gives a systematic view of metabolic heterogeneity and indicates the values of metabolic expression subtypes as predictive, prognostic, and therapeutic markers. In the second category, we design data-adaptive and pathway-based large-sample score test methods for association studies between somatic mutations and germline variations. A combination of multiple statistical techniques is used. Extensive information aggregation at both SNP and gene levels is involved. p-values from different parameters are combined to yield data-adaptive tests for somatic mutations and germline variations. To avoid using too many parameters so as to reduce costs, a randomized low-rank parameter preselection strategy is proposed to predict parameters that are likely more effective. In comparison with some commonly used methods, our data-adaptive somatic mutations/germline variations test methods are much more flexible, can apply to multiple germline SNPs/genes/pathways, and generally have much higher statistical powers. The test models are applied to both simulations and real-world ICGC (International Cancer Genome Consortium) datasets. For the ICGC data, a sequence of filtering, screening, and processing techniques is applied, followed by extensive association studies with our models. Our studies systematically identify the associations between various germline variations and somatic mutations across different cancer types. Our research provides valuable statistical tools for cancer risk prediction. The work leads to deeper understanding of molecular mechanisms of specific cancer genes and brings new insights into the development of novel cancer therapy. Advisors/Committee Members: Scott, David W (advisor), Liang, Han (advisor), Wei, Peng (advisor).

Subjects/Keywords: Association studies; statistical tests; human cancers, metabolic expression subtypes; somatic mutations; germline variations

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APA (6^th Edition):

Chen, Z. (2019). Association Studies in Human Cancers: Metabolic Expression Subtypes and Somatic Mutations/Germline Variations. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/106172

Chicago Manual of Style (16^th Edition):

Chen, Zhongyuan. “Association Studies in Human Cancers: Metabolic Expression Subtypes and Somatic Mutations/Germline Variations.” 2019. Doctoral Dissertation, Rice University. Accessed January 22, 2021. http://hdl.handle.net/1911/106172.

MLA Handbook (7^th Edition):

Chen, Zhongyuan. “Association Studies in Human Cancers: Metabolic Expression Subtypes and Somatic Mutations/Germline Variations.” 2019. Web. 22 Jan 2021.

Vancouver:

Chen Z. Association Studies in Human Cancers: Metabolic Expression Subtypes and Somatic Mutations/Germline Variations. [Internet] [Doctoral dissertation]. Rice University; 2019. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1911/106172.

Council of Science Editors:

Chen Z. Association Studies in Human Cancers: Metabolic Expression Subtypes and Somatic Mutations/Germline Variations. [Doctoral Dissertation]. Rice University; 2019. Available from: http://hdl.handle.net/1911/106172

13. Garg, Sumedha. Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal.

Degree: PhD, 2019, University of Cambridge

URL: https://doi.org/10.17863/CAM.36638 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767736

► Primary aldosteronism (PA) accounts for 5-10% of all hypertension. One of the major causes of PA is sporadic formation of aldosterone-producing adenomas (APAs). These benign… (more)

▼ Primary aldosteronism (PA) accounts for 5-10% of all hypertension. One of the major causes of PA is sporadic formation of aldosterone-producing adenomas (APAs). These benign tumours develop in the cortical region of adrenal glands and autonomously secrete excessive amounts of aldosterone. This hormone increases sodium retention and water reabsorption by the kidneys, leading to high blood pressure. Landmark discoveries of somatic mutations in APAs led to better understanding of molecular mechanisms causing autonomous aldosterone secretion. The first mutations were found in KCNJ5, followed by ATP1A1, ATP2B3 and CACNA1D, all encoding cation-channels or transporters. Several in vitro studies showed disruption of cellular ion-balance leading to the phenotype of hyper-aldosterone secretion from APAs. Following our lab's discovery of initial four somatic mutations by whole exome sequencing, over 30 single-base change mutations have been reported in the CACNA1D gene, which encodes the a1 subunit of an L-type Ca2+ channel (LTCC), CaV1.3. Initial and several subsequent mutations cause electrophysiological gain-of-function with increased activation and/or slowed inactivation of CaV1.3. Prior to the discovery of these mutations, L-type Ca2+ channels were not considered important in regulation of aldosterone production. In the first part of my thesis, I investigated two of the mutations and showed that the gain-of-function results in increased aldosterone secretion from an adrenocortical carcinoma cell line, H295R, when transiently transfected with the mutants. I also showed that CaV1.3 can play a role in physiological aldosterone secretion, finding that CYP11B2 expression is reduced by 50% in the adrenals of CaV1.3 knockout mice. The discovery of mutations in CACNA1D led to a drug discovery challenge award from a pharmaceutical company in which high-throughput screening of CaV1.3-expressing cells was undertaken against the company's 1.8M compound library. I identified the adrenal isoforms of the channel's alpha and beta subunits (CACNA1D and CACNB2), and helped development of the stable HEK293 cell line used for screening. This led to 3 tool compounds (A, B & C) that were selective antagonists for CaV1.3 over another family member of the ion channels in high-throughput electrophysiological experiments using IonWorks Barracuda and QPatch platforms. I showed compound B to effectively inhibit aldosterone secretion in both H295R and primary adrenal cells isolated from a normal adrenal. This finding is a significant step in developing compound B further into a CaV1.3-selective drug for treating PA patients without cardiovascular side effects as in the case of existing dihydropyridine class of Ca2+ channel blockers. The second part of my thesis focused on genotyping and whole exome sequencing of 59 APAs from 52 patients, in order to identify further genes underlying primary aldosteronism. Mutations in previously reported genes were identified in 34 of the APAs (57.6%). CACNA1D was the most commonly mutated gene (20.3%) in this cohort,…

Subjects/Keywords: aldosterone; adenoma; somatic mutations; hypertension

…somatic mutations in APAs led to better understanding of molecular mechanisms causing autonomous… …APAs. Following our lab’s discovery of initial four somatic mutations by whole exome… …greatly enhanced when we ascertained that one of the 'private' somatic mutations found… …157 16 LIST OF TABLES Table 1: Reported somatic mutations in APAs… …31 Table 2: Reported prevalence of somatic mutations in different cohorts…

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Garg, S. (2019). Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.36638 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767736

Chicago Manual of Style (16^th Edition):

Garg, Sumedha. “Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 22, 2021. https://doi.org/10.17863/CAM.36638 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767736.

MLA Handbook (7^th Edition):

Garg, Sumedha. “Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal.” 2019. Web. 22 Jan 2021.

Vancouver:

Garg S. Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 22]. Available from: https://doi.org/10.17863/CAM.36638 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767736.

Council of Science Editors:

Garg S. Role of two genes, CACNA1D and CADM1, with common or rare mutations in aldosterone producing adenomas of the adrenal. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.36638 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767736

14. Bianchi, Joy J. Origin of somatic mutations in lymphoid cancers : role of the V(D)J recombinase : Origine des mutations somatiques dans les cancers lymphoïdes : rôle de la recombinase V(D)J.

Degree: Docteur es, Génétique, 2018, Sorbonne Paris Cité

URL: http://www.theses.fr/2018USPCB057

►

Les cancers lymphoïdes présentent fréquemment des aberrations chromosomiques. Dans les lymphocytes, cette instabilité génomique peut découler d'une activité anormale de la recombinase V(D)J (i.e. RAG… (more)

▼

Les cancers lymphoïdes présentent fréquemment des aberrations chromosomiques. Dans les lymphocytes, cette instabilité génomique peut découler d'une activité anormale de la recombinase V(D)J (i.e. RAG endonuclease), alors que des facteurs de réponse aux dommages à l'ADN (DDR), tels que les protéines Ataxia-telangiectasia mutated (ATM) et p53, sont connus pour empêcher l'apparition de réarrangements chromosomiques et la lymphomagénèse. Le but de ma thèse fut de tester la contribution relative de ces facteurs dans l'émergence des mutations somatiques dans le génome des lymphomes. Pour ce faire, j'ai réalisé du séquençage génome et transcriptome entier de différents lymphomes, issus de modèles murins génétiquement modifiés pour lesquels les activités RAG et DDR étaient altérées. Lors d'une première étude, j'ai identifié des lésions génomiques spécifiques et récurrentes, causées par l'activité « off-target » de RAG et, de manière plus surprenante, un pattern de réarrangements anormaux survenant en l'absence de RAG. J'ai mis en évidence un mécanisme de « Breakage-Fusion-Bridge », en l'absence de RAG, entrainant l'instabilité et l'amplification d'une région génomique s'étendant sur plusieurs mégabases. Plus encore, j'ai également montré que cette amplification mène à son tour à la surexpression de multiples gènes connus ou candidats dans le cancer et se retrouve dans un sous-groupe de leucémies humaines. Afin de rétablir la différentiation des cellules T, bloquée en l'absence des RAG, j'ai utilisé un autre modèle murin exprimant un récepteur des cellules T (TCR) transgéniques. Ce travail a permis de montrer que le stade du développement et l'activité RAG tous les deux déterminent le paysage génomique des lymphomes T et guident la transformation maligne des cellules à travers différentes voies oncogéniques. De plus, j'ai également réalisé la première étude génome entier de lymphomes T déficients pour ATM et ai identifié un nombre important d'anomalies dans ces tumeurs, présentes aux loci des récepteurs aux antigènes mais aussi à des positions ectopiques. Mes résultats suggèrent, qu'en l'absence d'ATM, les cassures de l'ADN induites par les RAG (non réparées ou résolues de manière anormales) déclenchent une instabilité massive au niveau des loci des récepteurs aux antigènes. Cette instabilité se propage ensuite ailleurs dans le génome et affecte des gènes du cancer. De manière plus générale, ma thèse approfondie la compréhension des mécanismes générant des mutations somatiques dans les cancers lymphoïdes, suite à des défauts de recombinaison V(D)J ou de DDR.

Lymphoid cancers frequently harbor chromosomal aberrations. Abnormal V(D)J recombinase (i.e RAG endonuclease) activity is thought to promote genomic instability in lymphocytes, while DNA damage response (DDR) factors such as Ataxia-telangiectasia mutated (ATM) and p53 have been shown to suppress aberrant chromosomal rearrangements and lymphomagenesis. During my thesis, to test the relative contribution of these factors in shaping the pattern of somatic mutations in…

Advisors/Committee Members: Deriano, Ludovic (thesis director).

Subjects/Keywords: Instabilité génomique; Cancers lymphoïdes; Mutations somatiques; RAG recombinase; DNA damage response; Genomic instability; Lymphoid cancers; Somatic mutations; RAG recombinase; DNA damage response; 616.994

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bianchi, J. J. (2018). Origin of somatic mutations in lymphoid cancers : role of the V(D)J recombinase : Origine des mutations somatiques dans les cancers lymphoïdes : rôle de la recombinase V(D)J. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCB057

Chicago Manual of Style (16^th Edition):

Bianchi, Joy J. “Origin of somatic mutations in lymphoid cancers : role of the V(D)J recombinase : Origine des mutations somatiques dans les cancers lymphoïdes : rôle de la recombinase V(D)J.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 22, 2021. http://www.theses.fr/2018USPCB057.

MLA Handbook (7^th Edition):

Bianchi, Joy J. “Origin of somatic mutations in lymphoid cancers : role of the V(D)J recombinase : Origine des mutations somatiques dans les cancers lymphoïdes : rôle de la recombinase V(D)J.” 2018. Web. 22 Jan 2021.

Vancouver:

Bianchi JJ. Origin of somatic mutations in lymphoid cancers : role of the V(D)J recombinase : Origine des mutations somatiques dans les cancers lymphoïdes : rôle de la recombinase V(D)J. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Jan 22]. Available from: http://www.theses.fr/2018USPCB057.

Council of Science Editors:

Bianchi JJ. Origin of somatic mutations in lymphoid cancers : role of the V(D)J recombinase : Origine des mutations somatiques dans les cancers lymphoïdes : rôle de la recombinase V(D)J. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCB057

Freie Universität Berlin

15. Lüth, Maria. Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors.

Degree: 2011, Freie Universität Berlin

URL: https://refubium.fu-berlin.de/handle/fub188/13747

► To detect somatic mitochondrial DNA mutations in neuroectodermal tumors, mutation analysis in patients with medulloblastoma, pilocytic astrocytoma and neurofibromatosis type 1-associated tumors was performed. MtDNA… (more)

▼ To detect somatic mitochondrial DNA mutations in neuroectodermal tumors, mutation analysis in patients with medulloblastoma, pilocytic astrocytoma and neurofibromatosis type 1-associated tumors was performed. MtDNA alterations in the entire mitochondrial genome were analyzed by temporal temperature gradient gelelectrophoresis followed by DNA sequencing. We have analyzed the entire mitochondrial genome in 15 cases of medulloblastoma and the corresponding cerebrospinal fluid (CSF) samples in 10 of the 15 cases. Six of the fifteen cases (40%) showed at least one mtDNA mutation in the tumors. A total of 18 somatic mtDNA mutations were detected with one of the tumors having 11 mutations of which 9 were novel. Three of the six cases with mtDNA mutation also showed mutation in the cell-free CSF collected at various times during therapy. Somatic mtDNA mutations in tumors were found in 7 of 19 individuals with cutaneous neurofibromas and in 9 of 18 patients with plexiform neurofibromas. A total of 34 somatic mtDNA mutations were found. All mutations were located in the displacement loop region of the mitochondrial genome. Several plexiform neurofibromas from individual patients had multiple homoplasmic mtDNA mutations. In cutaneous neurofibromas, the same mtDNA mutations were always present in tumors from different locations of the same individual. An increase in the proportion of the mutant mtDNA was always found in the neurofibromas when compared with nontumor tissues. The somatic mtDNA mutations were present in the Schwann cells of the analyzed multiple cutaneous neurofibromas of the same individual. The observed dominance of a single mtDNA mutation in multiple cutaneous neurofibromas of individual patients indicates a common tumor cell ancestry and suggests a replicative advantage rather than random segregation for cells carrying these mutated mitochondria. Advisors/Committee Members: [email protected] (contact), w (gender), PD Dr. med. P. Hernáiz-Driever (firstReferee), Prof. Dr. med. M. Hasselblatt (furtherReferee), Prof. Dr. med. F. Aksu (furtherReferee).

Subjects/Keywords: mtDNA; somatic mutations; neurofibromatosis type 1-associated tumors; pilocytic astrocytoma; medulloblastoma; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lüth, M. (2011). Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors. (Thesis). Freie Universität Berlin. Retrieved from https://refubium.fu-berlin.de/handle/fub188/13747

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lüth, Maria. “Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors.” 2011. Thesis, Freie Universität Berlin. Accessed January 22, 2021. https://refubium.fu-berlin.de/handle/fub188/13747.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lüth, Maria. “Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors.” 2011. Web. 22 Jan 2021.

Vancouver:

Lüth M. Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors. [Internet] [Thesis]. Freie Universität Berlin; 2011. [cited 2021 Jan 22]. Available from: https://refubium.fu-berlin.de/handle/fub188/13747.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lüth M. Analysis of mitochondrial DNA mutations in patients with neuroectodermal tumors. [Thesis]. Freie Universität Berlin; 2011. Available from: https://refubium.fu-berlin.de/handle/fub188/13747

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

16. Blokzijl, Francis. Decoding the mutational history of human stem cells : From patterns to mechanisms.

Degree: 2018, University Utrecht

URL: https://dspace.library.uu.nl/handle/1874/371910 ; URN:NBN:NL:UI:10-1874-371910 ; urn:isbn:978-94-6375-173-5 ; URN:NBN:NL:UI:10-1874-371910 ; https://dspace.library.uu.nl/handle/1874/371910

► The extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of adult stem cell (ASC) divisions, owing to… (more)

▼ The extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of adult stem cell (ASC) divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal human ASCs remain unknown. In this thesis, a new method is presented for cataloging mutations in individual human ASCs. Single ASCs are expanded in vitro into clonal organoid cultures to generate sufficient DNA for whole-genome sequencing (WGS) analysis, which allows detection of the mutations that accumulated in vivo in the original ACS. Using this method, we determined the genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. However, mutational signature analysis suggests that different mutational processes contribute to mutation accumulation in liver ASCs compared to colon and small intestinal ASCs. In the intestinal ASCs the majority of the mutations are a result of spontaneous deamination of methylated cytosine residues. In liver, a mutational signature with an as-yet-unknown underlying mechanism is predominant. In addition to adult stem cells, we directly measured the base substitutions that have accumulated in single stem cells of second-trimester human fetuses in the liver and intestine. We detected on average ~48 somatic base substitutions per fetal stem cell, indicating that the mutation accumulation rate is at least 5-fold higher during fetal development than during postnatal life. Furthermore, stem cells of the fetal liver and intestine show distinct mutational profiles, suggesting that different DNA damage and/or repair mechanisms are at play in these tissues during development. Intriguingly, the mutational landscape of the fetal intestinal stem cells closely resembled that observed in intestinal ASCs from postnatal tissue. We used the CRISPR-Cas9 gene-editing technology to delete key DNA repair genes in human colon organoids and asses the mutational consequences in vitro. We found that organoids deficient in base excision repair harbor a mutational footprint similar to signature 30, which is previously observed in a breast cancer cohort. Furthermore, nucleotide excision repair (NER) deficient ASCs show an increased contribution of Signature 8 mutations, which is a pattern with unknown etiology that is recurrently observed in human cancers. The presence of these signatures in cancer genomes could hold diagnostic and prognostic value, and may improve personalized cancer treatment strategies.. For example, tumors deficient in NER are more sensitive to cisplatin treatment. Advisors/Committee Members: Cuppen, Edwin, van Boxtel, Ruben.

Subjects/Keywords: Whole genome sequencing; Somatic mutations; Stem cells; Organoids; Cancer

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APA (6^th Edition):

Blokzijl, F. (2018). Decoding the mutational history of human stem cells : From patterns to mechanisms. (Doctoral Dissertation). University Utrecht. Retrieved from https://dspace.library.uu.nl/handle/1874/371910 ; URN:NBN:NL:UI:10-1874-371910 ; urn:isbn:978-94-6375-173-5 ; URN:NBN:NL:UI:10-1874-371910 ; https://dspace.library.uu.nl/handle/1874/371910

Chicago Manual of Style (16^th Edition):

Blokzijl, Francis. “Decoding the mutational history of human stem cells : From patterns to mechanisms.” 2018. Doctoral Dissertation, University Utrecht. Accessed January 22, 2021. https://dspace.library.uu.nl/handle/1874/371910 ; URN:NBN:NL:UI:10-1874-371910 ; urn:isbn:978-94-6375-173-5 ; URN:NBN:NL:UI:10-1874-371910 ; https://dspace.library.uu.nl/handle/1874/371910.

MLA Handbook (7^th Edition):

Blokzijl, Francis. “Decoding the mutational history of human stem cells : From patterns to mechanisms.” 2018. Web. 22 Jan 2021.

Vancouver:

Blokzijl F. Decoding the mutational history of human stem cells : From patterns to mechanisms. [Internet] [Doctoral dissertation]. University Utrecht; 2018. [cited 2021 Jan 22]. Available from: https://dspace.library.uu.nl/handle/1874/371910 ; URN:NBN:NL:UI:10-1874-371910 ; urn:isbn:978-94-6375-173-5 ; URN:NBN:NL:UI:10-1874-371910 ; https://dspace.library.uu.nl/handle/1874/371910.

Council of Science Editors:

Blokzijl F. Decoding the mutational history of human stem cells : From patterns to mechanisms. [Doctoral Dissertation]. University Utrecht; 2018. Available from: https://dspace.library.uu.nl/handle/1874/371910 ; URN:NBN:NL:UI:10-1874-371910 ; urn:isbn:978-94-6375-173-5 ; URN:NBN:NL:UI:10-1874-371910 ; https://dspace.library.uu.nl/handle/1874/371910

17. Vijayan, Vinaya. Understanding and Improving Identification of Somatic Variants.

Degree: PhD, Genetics, Bioinformatics, and Computational Biology, 2016, Virginia Tech

URL: http://hdl.handle.net/10919/72969

► It is important to understand the entire spectrum of somatic variants to gain more insight into mutations that occur in different cancers for development of… (more)

▼ It is important to understand the entire spectrum of somatic variants to gain more insight into mutations that occur in different cancers for development of better diagnostic, prognostic and therapeutic tools. This thesis outlines our work in understanding somatic variant calling, improving the identification of somatic variants from whole genome and whole exome platforms and identification of biomarkers for lung cancer. Integrating somatic variants from whole genome and whole exome platforms poses a challenge as variants identified in the exonic regions of the whole genome platform may not be identified on the whole exome platform and vice-versa. Taking a simple union or intersection of the somatic variants from both platforms would lead to inclusion of many false positives (through union) and exclusion of many true variants (through intersection). We develop the first framework to improve the identification of somatic variants on whole genome and exome platforms using a machine learning approach by combining the results from two popular somatic variant callers. Testing on simulated and real data sets shows that our framework identifies variants more accurately than using only one somatic variant caller or using variants from only one platform. Short tandem repeats (STRs) are repetitive units of 2-6 nucleotides. STRs make up approximately 1% of the human genome and have been traditionally used as genetic markers in population studies. We conduct a series of in silico analyses using the exome data of 32 individuals with lung cancer to identify 103 STRs that could potentially serve as cancer diagnostic markers and 624 STRs that could potentially serve as cancer predisposition markers. Overall these studies improve the accuracy in identification of somatic variants and highlight the association of STRs to lung cancer. Advisors/Committee Members: Zhang, Liqing (committeechair), Wu, Xiaowei (committee member), Heath, Lenwood S. (committee member), Franck, Christopher T. (committee member).

Subjects/Keywords: Somatic variants; Somatic variant callers; Somatic point mutations; Short tandem repeat variation; Lung squamous cell carcinoma

…in detecting somatic point mutations in exomes 32 Figure 2.2: Sensitivity, precision and… …F1 score of different pipelines detecting somatic point mutations in genomes 33 Figure 2.3… …Factors affecting the detection of somatic point mutations. 34 Figure 2.4: Sensitivity of… …different pipelines in detecting somatic point mutations using a high quality exome data set 35… …pipelines while detecting somatic point mutations in exomes 36 Figure 2.6: Sensitivity as a…

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APA (6^th Edition):

Vijayan, V. (2016). Understanding and Improving Identification of Somatic Variants. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/72969

Chicago Manual of Style (16^th Edition):

Vijayan, Vinaya. “Understanding and Improving Identification of Somatic Variants.” 2016. Doctoral Dissertation, Virginia Tech. Accessed January 22, 2021. http://hdl.handle.net/10919/72969.

MLA Handbook (7^th Edition):

Vijayan, Vinaya. “Understanding and Improving Identification of Somatic Variants.” 2016. Web. 22 Jan 2021.

Vancouver:

Vijayan V. Understanding and Improving Identification of Somatic Variants. [Internet] [Doctoral dissertation]. Virginia Tech; 2016. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10919/72969.

Council of Science Editors:

Vijayan V. Understanding and Improving Identification of Somatic Variants. [Doctoral Dissertation]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/72969

East Carolina University

18. Nopparat, Jongdee. [Delta]-catenin: implications in prostate cancer progression.

Degree: PhD, Anatomy and Cell Biology, 2014, East Carolina University

URL: http://hdl.handle.net/10342/4436

► Prostate cancer (PCa) is the most commonly diagnosed cancer and the second most common cause of cancer death among men in the US. Due to… (more)

▼ Prostate cancer (PCa) is the most commonly diagnosed cancer and the second most common cause of cancer death among men in the US. Due to the advances in research, the ability to detect and cure PCa has improved and led to significant reductions in PCa patients' mortality. Therefore, determining and understanding specific molecular mechanisms involved in PCa progression is a pivotal step towards the potentially better and more accurate diagnosis and intervention of PCa in the future. [Delta]-catenin is a unique armadillo (Arm) domain containing protein in that it is neural specific and primarily expressed in the brain. However, [delta]-catenin alterations have been implicated in pathogenesis ranging from neuronal deficits, genetic disorders, to cancers. In particular, [delta]-catenin expression is shown to increase in primary human prostatic adenocarcinomas corresponding with PCa progression. Although overexpressed [delta]-catenin in PCa has been reported over a decade ago, few studies have been undertaken to identify how [delta]-catenin promotes PCa progression and what other significant molecules are relevant to its expression. Studies presented in this dissertation explore the effects of a truncated variant of [delta]-catenin involved in promoting PCa using both in vitro PCa culture systems and in vivo mouse models of PCa. Additionally, we aim to test the hypothesis that [delta]-catenin mutations promote PCa progression by interacting with multiple cancer-specific pathways including Î²-catenin/LEF-1-mediated transcription and HIF-1Î±. Information presented in this dissertation demonstrates that ectopic [delta]-catenin gene is susceptible to mutagenesis when overexpressed in PCa cells, CWR22Rv-1 and PC-3, leading to sequence disruptions predicting functional alterations. It is shown that PCa cells overexpressing mutant [delta]-catenin increase Î²-catenin translocation to the nucleus and HIF-1Î±; expression when cultured under glucose deprived condition. These results suggest that [delta]-catenin mutations provide a survival advantage upon overgrowth and glucose deprivation over the control cells. Furthermore, we demonstrate that [delta]-catenin mutations promote tumor development in mouse prostate with probasin promoter (ARRâ‚‚PB)-driven, prostate specific expression of Myc oncogene. Additional investigations indicate that [delta]-catenin mutations in Myc transgenic mice not only promote Î²-catenin expression leading to dramatically elevated Myc expression but HIF-1Î±; is also increased in a [delta]-catenin gene-dosage dependent manner. Overall, we reveal that the introduction Î²-catenin mutations is an important step in metabolic adaptation by modulating Î²-catenin and HIF-1Î±; signaling in order to magnify its tumor promoting effect Advisors/Committee Members: Chen, Yan-Hua (advisor).

Subjects/Keywords: Biology, Molecular; [Delta]-catenin; Glucose deprivation; Prostate – Cancer; Somatic mutations; Transgenic mouse models; Î´-catenin; Molecular biology; Prostatic Neoplasms – diagnosis; Catenins – metabolism; Adenocarcinomas – diagnosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nopparat, J. (2014). [Delta]-catenin: implications in prostate cancer progression. (Doctoral Dissertation). East Carolina University. Retrieved from http://hdl.handle.net/10342/4436

Chicago Manual of Style (16^th Edition):

Nopparat, Jongdee. “[Delta]-catenin: implications in prostate cancer progression.” 2014. Doctoral Dissertation, East Carolina University. Accessed January 22, 2021. http://hdl.handle.net/10342/4436.

MLA Handbook (7^th Edition):

Nopparat, Jongdee. “[Delta]-catenin: implications in prostate cancer progression.” 2014. Web. 22 Jan 2021.

Vancouver:

Nopparat J. [Delta]-catenin: implications in prostate cancer progression. [Internet] [Doctoral dissertation]. East Carolina University; 2014. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10342/4436.

Council of Science Editors:

Nopparat J. [Delta]-catenin: implications in prostate cancer progression. [Doctoral Dissertation]. East Carolina University; 2014. Available from: http://hdl.handle.net/10342/4436

University of Lund

19. Ravi, Naveen. Genetic Characterization and Identification of Novel Treatment Targets in Anaplastic Thyroid Carcinoma.

Degree: 2019, University of Lund

URL: https://lup.lub.lu.se/record/b2b10075-1aea-4976-92c0-5798c5163b81 ; https://portal.research.lu.se/ws/files/71276156/Naveen_Ravi_ALL.pdf

► Anaplastic thyroid cancer (ATC) is a rare and highly aggressive thyroid malignancy, usually resistant to conventional therapeutic strategies. The prognosis of ATC is extremely poor… (more)

▼ Anaplastic thyroid cancer (ATC) is a rare and highly aggressive thyroid malignancy, usually resistant to conventional therapeutic strategies. The prognosis of ATC is extremely poor with a median survival rate of 6 months. Current treatment therapy includes surgical resection in combination with external radiotherapy and chemotherapy. The underlying mechanisms involved in ATC tumorigenesis is understudied. In this thesis, we have focused on genomic characterization of ATC that could possibly lead to identification of novel treatment strategies in ATC.Article I & III highlights the genomic heterogeneity in ATC cell lines and primary cases. ATC displayed massive aneuploidy with frequent variations in copy number. Additionally, we found frequent mutations in TP53, TERT, BRAF and RAS family genes. Furthermore, the most frequent mutational signature in ATC cell lines and primary cases was increased activity of the cytidine deaminase apolipoprotein B editing complex (APOBEC). Moreover, we found interstitial deletions in NEGR1, resulting in aberrant splicing, which could possibly be a driver event in ATC. Furthermore, we detected amplifications in CCNE1, CDK6 and TWIST1; these patients could be treated with targeted therapy. In Article II, we investigated the tumor initiation, progression and clonal evolution of papillary thyroid cancer in a conditional mouse model. Stochastic activation of mutant Braf leads to development of multifocal microtumors that are oligoclonal in nature. Furthermore, we identified additional mutations at low frequencies, highlighting the presence of subclones that might be associated with tumor progression. In article IV, we studied the genome-wide methylation profile in primary ATC cases. Global hypomethylation was common in ATC, while hypermethylation was noticed in promoters and CpG islands. Furthermore, aberrant DNA methylation in MTOR and NOTCH1 genes was associated with increased expression. Alternatively, hypomethylation in thyroid related genes including TSHR and SLC26A7 was associated with decreased expression in gene body regions. Moreover, we found that processes related to the cell cycle were upregulated, while TP53-regulated genes and thyroid-related pathways were downregulated in ATC.Taken together, this thesis provides a better understanding of the complex processes involved in ATC tumorigenesis. Furthermore, a substantial proportion of ATC patients could be suitable for personalized treatment, including CDK and TWIST1 inhibition therapy.

Subjects/Keywords: Cancer and Oncology; Cell and Molecular Biology; Anaplastic thyroid cancer; copy number alterations; somatic mutations; mutational signatures; DNA methylation analysis; Gene expression analysis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ravi, N. (2019). Genetic Characterization and Identification of Novel Treatment Targets in Anaplastic Thyroid Carcinoma. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/b2b10075-1aea-4976-92c0-5798c5163b81 ; https://portal.research.lu.se/ws/files/71276156/Naveen_Ravi_ALL.pdf

Chicago Manual of Style (16^th Edition):

Ravi, Naveen. “Genetic Characterization and Identification of Novel Treatment Targets in Anaplastic Thyroid Carcinoma.” 2019. Doctoral Dissertation, University of Lund. Accessed January 22, 2021. https://lup.lub.lu.se/record/b2b10075-1aea-4976-92c0-5798c5163b81 ; https://portal.research.lu.se/ws/files/71276156/Naveen_Ravi_ALL.pdf.

MLA Handbook (7^th Edition):

Ravi, Naveen. “Genetic Characterization and Identification of Novel Treatment Targets in Anaplastic Thyroid Carcinoma.” 2019. Web. 22 Jan 2021.

Vancouver:

Ravi N. Genetic Characterization and Identification of Novel Treatment Targets in Anaplastic Thyroid Carcinoma. [Internet] [Doctoral dissertation]. University of Lund; 2019. [cited 2021 Jan 22]. Available from: https://lup.lub.lu.se/record/b2b10075-1aea-4976-92c0-5798c5163b81 ; https://portal.research.lu.se/ws/files/71276156/Naveen_Ravi_ALL.pdf.

Council of Science Editors:

Ravi N. Genetic Characterization and Identification of Novel Treatment Targets in Anaplastic Thyroid Carcinoma. [Doctoral Dissertation]. University of Lund; 2019. Available from: https://lup.lub.lu.se/record/b2b10075-1aea-4976-92c0-5798c5163b81 ; https://portal.research.lu.se/ws/files/71276156/Naveen_Ravi_ALL.pdf

Kyoto University / 京都大学

20. Sawai, Yugo. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations : Activation-induced cytidine deaminaseは腫瘍関連遺伝子に変異を誘導することにより膵腫瘍形成に寄与する.

Degree: 博士(医学), 2016, Kyoto University / 京都大学

URL: http://hdl.handle.net/2433/215393 ; http://dx.doi.org/10.14989/doctor.k19567

新制・課程博士

甲第19567号

医博第4074号

Subjects/Keywords: Activation-induced cytidine deaminase; Pancreatic cancer; Acinar-ductal metaplasia; Pancreatic intraepithelial neoplasia; Somatic mutations

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sawai, Y. (2016). Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations : Activation-induced cytidine deaminaseは腫瘍関連遺伝子に変異を誘導することにより膵腫瘍形成に寄与する. (Thesis). Kyoto University / 京都大学. Retrieved from http://hdl.handle.net/2433/215393 ; http://dx.doi.org/10.14989/doctor.k19567

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sawai, Yugo. “Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations : Activation-induced cytidine deaminaseは腫瘍関連遺伝子に変異を誘導することにより膵腫瘍形成に寄与する.” 2016. Thesis, Kyoto University / 京都大学. Accessed January 22, 2021. http://hdl.handle.net/2433/215393 ; http://dx.doi.org/10.14989/doctor.k19567.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sawai, Yugo. “Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations : Activation-induced cytidine deaminaseは腫瘍関連遺伝子に変異を誘導することにより膵腫瘍形成に寄与する.” 2016. Web. 22 Jan 2021.

Vancouver:

Sawai Y. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations : Activation-induced cytidine deaminaseは腫瘍関連遺伝子に変異を誘導することにより膵腫瘍形成に寄与する. [Internet] [Thesis]. Kyoto University / 京都大学; 2016. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2433/215393 ; http://dx.doi.org/10.14989/doctor.k19567.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sawai Y. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations : Activation-induced cytidine deaminaseは腫瘍関連遺伝子に変異を誘導することにより膵腫瘍形成に寄与する. [Thesis]. Kyoto University / 京都大学; 2016. Available from: http://hdl.handle.net/2433/215393 ; http://dx.doi.org/10.14989/doctor.k19567

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

21. Lianos, Georgios. Προγνωστικοί παράγοντες και εξατομικευμένη χειρουργική στον καρκίνο του στομάχου.

Degree: 2015, University of Ioannina; Πανεπιστήμιο Ιωαννίνων

URL: http://hdl.handle.net/10442/hedi/41927

►

GASTRIC CANCER CONSTITUTES THE FOURTH MOST COMMON TYPE OF CANCER AND THESECOND CAUSE OF DEATH RELATED WITH CANCER WORLDWIDE. THE AIM OF THIS THESISIS TO… (more)

▼

GASTRIC CANCER CONSTITUTES THE FOURTH MOST COMMON TYPE OF CANCER AND THESECOND CAUSE OF DEATH RELATED WITH CANCER WORLDWIDE. THE AIM OF THIS THESISIS TO IDENTIFY RISK FACTORS ASSOCIATED WITH POST-OPERATIVE COMPLICATIONSAFTER GASTRECTOMY AS WELL AS TO IDENTIFY PROGNOSTIC FACTORS FOR GASTRICCANCER. AN EFFORT IS ALSO MADE IN ORDER TO IDENTIFY WITH NEXT-GENERATIONSEQUENCING ANALYSES, POTENTIAL MUTATIONS, GENETIC POLYMORPHISMS AND NOVELGENES INVOLVED IN GASTRIC CARCINOGENESIS. OVERWEIGHT PATIENTS ARE IN HIGHRISK TO PRESENT POST-OPERATIVE COMPLICATIONS AFTER GASTRECTOMY. MOREOVER,HIGH BODY MASS INDEX AND LYMPH NODE RATIO ARE ASSOCIATED WITH POOR SURVIVALAFTER GASTRECTOMY. AS FOR OUR GENOMIC ANALYSES IN GASTRIC CANCER/NORMALTISSUES, A HIGH NUMBER OF NOVEL SINGLE NUCLEOTIDE POLYMORHISMS WASIDENTIFIED AND THE MOST COMMON TYPES OF SOMATIC MUTATIONS IN OUR PATIENTSWERE C:G-T:A MUTATIONS. WE HAVE ALSO CONFIRMED 4 GENES IDENTIFIED ALSO INSIMILAR ANALYSES FOR GASTRIC CANCER. NOTABLY, 28 GENES THAT MAYBE PLAY ANIMPORTANT ROLE IN GASTRIC CARCINOGENESIS WERE HIGHLIGHTED FOR THE FIRST TIMEIN OUR STUDY. IT IS CLEAR THAT GASTRIC CANCER REPRESENTS A COMPLEX ANDHETEROGENEOUS DISEASE. IDENTIFICATION OF SOMATIC MUTATIONS AND NOVEL GENESCOULD HAVE TWO FUTURE IMPLICATIONS. FIRSTY, THE IDENTIFICATION OF ROBUSTBIOMARKERS AND SECONDLY THE DISCOVERY OF NEXT GENERATION DRUGS. THESEFINDINGS RAISE IMPORTANT EXPECTATIONS FOR THE PERSONALIZED MANAGEMENT OFGASTRIC CANCER.

Ο ΚΑΡΚΙΝΟΣ ΤΟΥ ΣΤΟΜΑΧΟΥ ΑΠΟΤΕΛΕΙ ΤΗΝ ΤΕΤΑΡΤΗ ΠΙΟ ΣΥΧΝΗ ΚΑΚΟΗΘΕΙΑ ΚΑΙ ΤΗ ΔΕΥΤΕΡΗ ΠΙΟ ΣΥΧΝΗ ΑΙΤΙΑ ΘΑΝΑΤΟΥ ΣΧΕΤΙΖΟΜΕΝΗ ΜΕ ΚΑΡΚΙΝΟ ΠΑΓΚΟΣΜΙΩΣ. ΗΣΥΓΚΕΚΡΙΜΕΝΗ ΔΙΔΑΚΤΟΡΙΚΗ ΔΙΑΤΡΙΒΗ ΕΧΕΙ ΩΣ ΣΤΟΧΟ ΤΟΝ ΚΑΘΟΡΙΣΜΟ ΠΑΡΑΓΟΝΤΩΝ ΚΙΝΔΥΝΟΥ ΓΙΑ ΤΗΝ ΕΜΦΑΝΙΣΗ ΜΕΤΕΓΧΕΙΡΗΤΙΚΩΝ ΕΠΙΠΛΟΚΩΝ ΜΕΤΑ ΑΠΟ ΓΑΣΤΡΕΚΤΟΜΗΚΑΙ ΤΟΝ ΚΑΘΟΡΙΣΜΟ ΠΡΟΓΝΩΣΤΙΚΩΝ ΠΑΡΑΓΟΝΤΩΝ ΣΤΟΝ ΚΑΡΚΙΝΟ ΤΟΥ ΣΤΟΜΑΧΟΥ. ΕΠΕΙΤΑ ΓΙΝΕΤΑΙ ΠΡΟΣΠΑΘΕΙΑ ΑΝΕΥΡΕΣΗΣ, ΜΕΣΩ ΑΝΑΛΥΣΗΣ ΓΟΝΙΔΙΩΜΑΤΟΣ ΜΕΤΕΧΝΟΛΟΓΙΕΣ ΕΠΟΜΕΝΗΣ ΓΕΝΙΑΣ, ΜΕΤΑΛΛΑΞΕΩΝ, ΠΟΛΥΜΟΡΦΙΣΜΩΝ, ΝΕΩΝ ΓΟΝΙΔΙΩΝΣΤΟΝ ΚΑΡΚΙΝΟ ΤΟΥ ΣΤΟΜΑΧΟΥ. ΟΙ ΥΠΕΡΒΑΡΟΙ ΑΣΘΕΝΕΙΣ ΜΕ ΚΑΡΚΙΝΟ ΣΤΟΜΑΧΟΥ ΒΡΕΘΗΚΕ ΟΤΙ ΠΑΡΟΥΣΙΑΖΟΥΝ ΑΥΞΗΜΕΝΟ ΚΙΝΔΥΝΟ ΕΜΦΑΝΙΣΗΣ ΜΕΤΕΓΧΕΙΡΗΤΙΚΩΝ ΕΠΙΠΛΟΚΩΝ ΜΕΤΑ ΑΠΟ ΓΑΣΤΡΕΚΤΟΜΗ. ΕΠΙΠΛΕΟΝ, Ο ΥΨΗΛΟΣ ΔΕΙΚΤΗΣ ΜΑΖΑΣ-ΣΩΜΑΤΟΣΚΑΙ Η ΑΝΑΛΟΓΙΑ ΤΩΝ ΔΙΗΘΗΜΕΝΩΝ ΛΕΜΦΑΔΕΝΩΝ ΑΠΟΤΕΛΟΥΝ ΔΕΙΚΤΕΣ ΦΤΩΧΗΣ ΕΠΙΒΙΩΣΗΣ ΣΕ ΑΣΘΕΝΕΙΣ ΜΕ ΚΑΡΚΙΝΟ ΣΤΟΜΑΧΟΥ. ΟΣΟΝ ΑΦΟΡΑ ΤΗ ΓΟΝΙΔΙΩΜΑΤΙΚΗ ΑΝΑΛΥΣΗ ΣΕ ΓΑΣΤΡΙΚΟΥΣ ΚΑΡΚΙΝΙΚΟΥΣ/ΦΥΣΙΟΛΟΓΙΚΟΥΣ ΙΣΤΟΥΣ, ΑΝΕΥΡΕΘΗΚΑΝ ΠΟΛΛΟΙ ΝΕΟΙ ΝΟΥΚΛΕΟΤΙΔΙΚΟΙ ΠΟΛΥΜΟΡΦΙΣΜΟΙ ΚΑΙ ΠΡΟΕΚΥΨΕ ΟΤΙ ΟΙ ΠΙΟ ΣΥΧΝΕΣ ΜΕΤΑΛΛΑΞΕΙΣ ΣΤΟΥΣ ΑΣΘΕΝΕΙΣ ΜΑΣ ΗΤΑΝ ΟΙ ΜΕΤΑΛΛΑΞΕΙΣ C:G-T:A. ΕΠΙΒΕΒΑΙΩΣΑΜΕ 4 ΓΟΝΙΔΙΑ ΠΟΥ ΑΝΕΥΡΕΘΗΚΑΝ ΣΕ ΠΑΡΟΜΟΙΕΣ ΑΝΑΛΥΣΕΙΣ ΑΣΘΕΝΩΝ ΜΕ ΚΑΡΚΙΝΟ ΣΤΟΜΑΧΟΥ. ΕΠΙΠΛΕΟΝ ΑΝΕΥΡΕΘΗΚΑΝ ΓΙΑ ΠΡΩΤΗ ΦΟΡΑ ΣΤΗΝ ΜΕΛΕΤΗ ΜΑΣ 28 ΓΟΝΙΔΙΑ ΠΟΥ ΙΣΩΣ ΝΑ ΔΙΑΔΡΑΜΑΤΙΖΟΥΝ ΣΗΜΑΝΤΙΚΟ ΡΟΛΟ ΣΤΗ ΓΑΣΤΡΙΚΗ ΚΑΡΚΙΝΟΓΕΝΕΣΗ. ΔΙΑΦΑΙΝΕΤΑΙ Η ΠΟΛΥΠΛΟΚΟΤΗΤΑ ΚΑΙ Η ΕΤΕΡΟΓΕΝΕΙΑ ΤΟΥ ΓΑΣΤΡΙΚΟΥ ΚΑΡΚΙΝΟΥ. Η ΑΝΙΧΝΕΥΣΗ ΣΩΜΑΤΙΚΩΝ ΜΕΤΑΛΛΑΞΕΩΝ ΚΑΙ ΝΕΩΝ ΓΟΝΙΔΙΩΝ ΜΠΟΡΕΙ ΝΑ ΕΧΕΙ ΣΤΟ ΜΕΛΛΟΝ ΔΥΟ ΕΦΑΡΜΟΓΕΣ. ΠΡΩΤΟΝ ΤΗΝ ΑΝΑΚΑΛΥΨΗ ΙΣΧΥΡΩΝ ΒΙΟΔΕΙΚΤΩΝ ΚΑΙ ΔΕΥΤΕΡΟΝ ΤΗΝ ΑΝΑΚΑΛΥΨΗ ΦΑΡΜΑΚΩΝ ΕΠΟΜΕΝΗΣ ΓΕΝΙΑΣ. ΟΛΑ ΑΥΤΑ ΤΑ ΔΕΔΟΜΕΝΑ ΠΑΡΕΧΟΥΝ ΒΑΣΙΜΕΣ ΠΡΟΣΔΟΚΙΕΣ ΓΙΑ ΤΗΝ ΕΞΑΤΟΜΙΚΕΥΜΕΝΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΣΤΟΝ…

Subjects/Keywords: Καρκίνος στομάχου; Προγνωστικοί παράγοντες; Εξατομικευμένη ιατρική; Βιοδείκτες; Ανάλυση γονιδιώματος; Τεχνολογίες επόμενης γενιάς; Γονίδια; Σωματικές μεταλλάξεις; Gastric cancer; Prognostic factors; Personalized medicine; Biomarkers; Genome analyses; Next generation sequencing analyses; Somatic mutations; Genes

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APA (6^th Edition):

Lianos, G. (2015). Προγνωστικοί παράγοντες και εξατομικευμένη χειρουργική στον καρκίνο του στομάχου. (Thesis). University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Retrieved from http://hdl.handle.net/10442/hedi/41927

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lianos, Georgios. “Προγνωστικοί παράγοντες και εξατομικευμένη χειρουργική στον καρκίνο του στομάχου.” 2015. Thesis, University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Accessed January 22, 2021. http://hdl.handle.net/10442/hedi/41927.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lianos, Georgios. “Προγνωστικοί παράγοντες και εξατομικευμένη χειρουργική στον καρκίνο του στομάχου.” 2015. Web. 22 Jan 2021.

Vancouver:

Lianos G. Προγνωστικοί παράγοντες και εξατομικευμένη χειρουργική στον καρκίνο του στομάχου. [Internet] [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2015. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10442/hedi/41927.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lianos G. Προγνωστικοί παράγοντες και εξατομικευμένη χειρουργική στον καρκίνο του στομάχου. [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2015. Available from: http://hdl.handle.net/10442/hedi/41927

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

22. Theil, Jan. The role of somatic mutations in the non-coding region of the rearranged immunoglobulin gene in Hodgkin Reed-Sternberg cells for silenced immunoglobulin gene expression in classical Hodgkins disease.

Degree: 2003, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-8062

► The absence of immunoglobulin (Ig) expression in B-cell derived Hodgkin Reed- Sternberg cells of classical Hodgkins disease, has been suggested to be caused by crippling… (more)

▼ The absence of immunoglobulin (Ig) expression in B-cell derived Hodgkin Reed- Sternberg cells of classical Hodgkins disease, has been suggested to be caused by crippling mutations in the Ig coding region and more recently in the Ig promoter region. This study addressed the role of mutations in the Ig promoter region to prevent Ig expression in HRS cells. 335 single isolated Hodgkin Reed-Sternberg cells from nine cases of classical Hodgkins disease and four B-cell derived Hodgkin cell lines, were analyzed for mutations in the TATA box and octamer motif of the Ig promoter. Furthermore, we investigated the octamer motif of the Eµ-Enhancers exclusively in the Hodgkin cell lines. The enhancer octamer motives and the TATA boxes were completely unaffected. Mutations of the promoter octamer motif were found in only one of nine cases and one of four Hodgkin cell lines. We also demonstrated that analysis of the complete Ig coding region (FW1-JH) fails to detect more crippling mutations as previously described. This supports the view that crippling mutations in the Ig promoter, the Ig coding region, and/or both may not contribute in most cases to the lack of Ig gene expression in Hodgkin Reed-Sternberg cells. To clarify whether or not the Ig gene transcription machinery might be defective in Hodgkin Reed- Sternberg cells, we analyzed in the Hodgkin cell lines, the important transcription factors Oct-1, Oct-2, and OCA-B at protein and m-RNA level. In contrast to controls, in all Hodgkin cell lines either a complete lack or strong reduction in the expression of the Oct-2 transcription factor and the OCA-B co- activator were found. The conclusions drawn from these results are that crippling mutations in the Ig gene promoter and coding region are not the sole cause for the lack of Ig expression in Hodgkin Reed-Sternberg cells. That defects of the transcription machinery such as absence of Oct-2/OCA-B are more important for this phenomenon in classical Hodgkins disease. Advisors/Committee Members: n (gender), Prof. Dr. Harald Stein (firstReferee), Prof. Dr. Karl Sperling (furtherReferee).

Subjects/Keywords: hodgkins disease; immunoglobulin; promoter; somatic mutations; transcription factor; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

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APA (6^th Edition):

Theil, J. (2003). The role of somatic mutations in the non-coding region of the rearranged immunoglobulin gene in Hodgkin Reed-Sternberg cells for silenced immunoglobulin gene expression in classical Hodgkins disease. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-8062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Theil, Jan. “The role of somatic mutations in the non-coding region of the rearranged immunoglobulin gene in Hodgkin Reed-Sternberg cells for silenced immunoglobulin gene expression in classical Hodgkins disease.” 2003. Thesis, Freie Universität Berlin. Accessed January 22, 2021. http://dx.doi.org/10.17169/refubium-8062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Theil, Jan. “The role of somatic mutations in the non-coding region of the rearranged immunoglobulin gene in Hodgkin Reed-Sternberg cells for silenced immunoglobulin gene expression in classical Hodgkins disease.” 2003. Web. 22 Jan 2021.

Vancouver:

Theil J. The role of somatic mutations in the non-coding region of the rearranged immunoglobulin gene in Hodgkin Reed-Sternberg cells for silenced immunoglobulin gene expression in classical Hodgkins disease. [Internet] [Thesis]. Freie Universität Berlin; 2003. [cited 2021 Jan 22]. Available from: http://dx.doi.org/10.17169/refubium-8062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Theil J. The role of somatic mutations in the non-coding region of the rearranged immunoglobulin gene in Hodgkin Reed-Sternberg cells for silenced immunoglobulin gene expression in classical Hodgkins disease. [Thesis]. Freie Universität Berlin; 2003. Available from: http://dx.doi.org/10.17169/refubium-8062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Queensland

23. Guo, Zeng. Histopathological, biochemical and genetic characterization of different types of primary aldosteronism, including validation of a new angiotensin assay.

Degree: Faculty of Medicine, 2020, University of Queensland

URL: https://espace.library.uq.edu.au/view/UQ:d835d46/thumbnail_s44091301_final_thesis_t.jpg ; https://espace.library.uq.edu.au/view/UQ:d835d46/s44091301_final_thesis.pdf ; https://espace.library.uq.edu.au/view/UQ:d835d46

Subjects/Keywords: Primary aldosteronism; Renin-angiotensin system; Mass spectrometry; Hybrid steroids; Somatic gene mutations; 1101 Medical Biochemistry and Metabolomics; 1103 Clinical Sciences

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APA (6^th Edition):

Guo, Z. (2020). Histopathological, biochemical and genetic characterization of different types of primary aldosteronism, including validation of a new angiotensin assay. (Thesis). University of Queensland. Retrieved from https://espace.library.uq.edu.au/view/UQ:d835d46/thumbnail_s44091301_final_thesis_t.jpg ; https://espace.library.uq.edu.au/view/UQ:d835d46/s44091301_final_thesis.pdf ; https://espace.library.uq.edu.au/view/UQ:d835d46

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Guo, Zeng. “Histopathological, biochemical and genetic characterization of different types of primary aldosteronism, including validation of a new angiotensin assay.” 2020. Thesis, University of Queensland. Accessed January 22, 2021. https://espace.library.uq.edu.au/view/UQ:d835d46/thumbnail_s44091301_final_thesis_t.jpg ; https://espace.library.uq.edu.au/view/UQ:d835d46/s44091301_final_thesis.pdf ; https://espace.library.uq.edu.au/view/UQ:d835d46.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Guo, Zeng. “Histopathological, biochemical and genetic characterization of different types of primary aldosteronism, including validation of a new angiotensin assay.” 2020. Web. 22 Jan 2021.

Vancouver:

Guo Z. Histopathological, biochemical and genetic characterization of different types of primary aldosteronism, including validation of a new angiotensin assay. [Internet] [Thesis]. University of Queensland; 2020. [cited 2021 Jan 22]. Available from: https://espace.library.uq.edu.au/view/UQ:d835d46/thumbnail_s44091301_final_thesis_t.jpg ; https://espace.library.uq.edu.au/view/UQ:d835d46/s44091301_final_thesis.pdf ; https://espace.library.uq.edu.au/view/UQ:d835d46.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Guo Z. Histopathological, biochemical and genetic characterization of different types of primary aldosteronism, including validation of a new angiotensin assay. [Thesis]. University of Queensland; 2020. Available from: https://espace.library.uq.edu.au/view/UQ:d835d46/thumbnail_s44091301_final_thesis_t.jpg ; https://espace.library.uq.edu.au/view/UQ:d835d46/s44091301_final_thesis.pdf ; https://espace.library.uq.edu.au/view/UQ:d835d46

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

24. Bos, C.J. Induced mutation and somatic recombination as tools for genetic analysis and breeding of imperfect fungi.

Degree: 1986, Landbouwhogeschool Wageningen

URL: http://library.wur.nl/WebQuery/wurpubs/1091 ; urn:nbn:nl:ui:32-1091 ; urn:nbn:nl:ui:32-1091 ; http://library.wur.nl/WebQuery/wurpubs/1091

► Many fungi which are important in Agriculture as plant pathogens or in Biotechnology as producers of organic acids, antibiotics or enzymes, are imperfect fungi. These… (more)

▼ Many fungi which are important in Agriculture as plant pathogens or in Biotechnology as producers of organic acids, antibiotics or enzymes, are imperfect fungi. These fungi do not have a sexual stage, which implies that they lack a meiotic recombination mechanism.However, many imperfect fungi have effective recombination mechanisms operating-during mitotic divisions. The first step in somatic recombination is the fusion of somatic cells. In nature this occurs by hyphal fusion followed by exchange of nuclei, which results in a heterokaryotic mycelium, if the partners are genetically different. Owing to fusion of somatic nuclei (karyogamy), which occurs at a very low frequency, heterozygous diploid nuclei may then arise. Heterozygous diploid strains can be isolated and maintained by transfer of conidia. During division of somatic nuclei (mitosis) recombination of genes can occur by mitotic crossing-over and by loss of chromosomes leading to haploid recombinants.In the laboratory heterozygous diploid strains can also be obtained via protoplast fusion.This study concerns the biotechnologically important fungus Aspergillus niger and the phytopathogenic fungus Colletotrichum lindemuthianum (the causal organism of bean anthracnose), whereas studies on fundamental aspects or on the development of procedures were carried out with the genetically well known fungus Aspergillus nidulans. The latter has both a sexual stage and well studied processes of somatic recombination. We used it as a model for studies on mutation induction, heterokaryosis and protoplast fusion.The chapter on induction and isolation of mutants (Chapter 2) presents studies on UV-survival curves for conidiospores (2.2), the frequency of mutants (2.3) and mutant enrichment procedures (2.4).The interpretation of the shape of survival curves was discussed. Processes generating an initial shoulder in logsurvival curves have quite different effects: A multi-hit process leads to a much more pronounced initial shoulder than a multi-target process does. In the experimental part is was argued that the initial shoulders in logS curves of haploid uninucleate A.nidulans conidiospores (single target cells) probably are the result of an inherent repair capacity which becomes saturated at a certain UV dose. An increase in target number (number of genomes in the spore) results in an increase of the logS-intercept due to a larger shoulder. At the same time, however, the repair capacity may have increased and complementation of lethal lesions may occur. In general such increases of the logS-intercept lead to overestimation of the target number.As in practice often high mutagen doses are applied so that mutants are isolated at low survival, the relationship between mutant frequency and survival was analyzed to see whether such high mutagen doses are necessary at all. High doses produce chromosome rearrangements and unnoticed mutations which disturb the genetic background. For several types of mutation it was shown that the highest yield of mutants is… Advisors/Committee Members: J.H. van der Veen.

Subjects/Keywords: deuteromycotina; somatische hybridisatie; verwijderde hybridisatie; geïnduceerde mutaties; Anamorfe schimmels; deuteromycotina; somatic hybridization; wide hybridization; induced mutations; Anamorphic Fungi

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APA (6^th Edition):

Bos, C. J. (1986). Induced mutation and somatic recombination as tools for genetic analysis and breeding of imperfect fungi. (Doctoral Dissertation). Landbouwhogeschool Wageningen. Retrieved from http://library.wur.nl/WebQuery/wurpubs/1091 ; urn:nbn:nl:ui:32-1091 ; urn:nbn:nl:ui:32-1091 ; http://library.wur.nl/WebQuery/wurpubs/1091

Chicago Manual of Style (16^th Edition):

Bos, C J. “Induced mutation and somatic recombination as tools for genetic analysis and breeding of imperfect fungi.” 1986. Doctoral Dissertation, Landbouwhogeschool Wageningen. Accessed January 22, 2021. http://library.wur.nl/WebQuery/wurpubs/1091 ; urn:nbn:nl:ui:32-1091 ; urn:nbn:nl:ui:32-1091 ; http://library.wur.nl/WebQuery/wurpubs/1091.

MLA Handbook (7^th Edition):

Bos, C J. “Induced mutation and somatic recombination as tools for genetic analysis and breeding of imperfect fungi.” 1986. Web. 22 Jan 2021.

Vancouver:

Bos CJ. Induced mutation and somatic recombination as tools for genetic analysis and breeding of imperfect fungi. [Internet] [Doctoral dissertation]. Landbouwhogeschool Wageningen; 1986. [cited 2021 Jan 22]. Available from: http://library.wur.nl/WebQuery/wurpubs/1091 ; urn:nbn:nl:ui:32-1091 ; urn:nbn:nl:ui:32-1091 ; http://library.wur.nl/WebQuery/wurpubs/1091.

Council of Science Editors:

Bos CJ. Induced mutation and somatic recombination as tools for genetic analysis and breeding of imperfect fungi. [Doctoral Dissertation]. Landbouwhogeschool Wageningen; 1986. Available from: http://library.wur.nl/WebQuery/wurpubs/1091 ; urn:nbn:nl:ui:32-1091 ; urn:nbn:nl:ui:32-1091 ; http://library.wur.nl/WebQuery/wurpubs/1091

Erasmus University Rotterdam

25. MacKenzie, Katherine. Hirschsprung Disease: development & treatment avenues: De ziekte van Hirschsprung: ontwikkeling & behandelingsmogelijkheden.

Degree: 2019, Erasmus University Rotterdam

URL: http://hdl.handle.net/1765/116709

► textabstractThe work of this thesis investigates the development of, and treatment options for, Hirschsprung disease (HSCR). We explore the missing heritability that is seen in… (more)

Subjects/Keywords: Hirschsprung disease; enteric nervous system; neural crest; somatic mutations; copy number variation; Goldberg-Shprintzen syndrome; KIF1BP; missense variations; cell replacement therapy

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APA (6^th Edition):

MacKenzie, K. (2019). Hirschsprung Disease: development & treatment avenues: De ziekte van Hirschsprung: ontwikkeling & behandelingsmogelijkheden. (Doctoral Dissertation). Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/116709

Chicago Manual of Style (16^th Edition):

MacKenzie, Katherine. “Hirschsprung Disease: development & treatment avenues: De ziekte van Hirschsprung: ontwikkeling & behandelingsmogelijkheden.” 2019. Doctoral Dissertation, Erasmus University Rotterdam. Accessed January 22, 2021. http://hdl.handle.net/1765/116709.

MLA Handbook (7^th Edition):

MacKenzie, Katherine. “Hirschsprung Disease: development & treatment avenues: De ziekte van Hirschsprung: ontwikkeling & behandelingsmogelijkheden.” 2019. Web. 22 Jan 2021.

Vancouver:

MacKenzie K. Hirschsprung Disease: development & treatment avenues: De ziekte van Hirschsprung: ontwikkeling & behandelingsmogelijkheden. [Internet] [Doctoral dissertation]. Erasmus University Rotterdam; 2019. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/1765/116709.

Council of Science Editors:

MacKenzie K. Hirschsprung Disease: development & treatment avenues: De ziekte van Hirschsprung: ontwikkeling & behandelingsmogelijkheden. [Doctoral Dissertation]. Erasmus University Rotterdam; 2019. Available from: http://hdl.handle.net/1765/116709

26. Akker, Peter Christiaan van den. Dystrophic epidermolysis bullosa: novel insights into the genotype-phenotype correlation and somatic mosaicism.

Degree: Faculteit Medische Wetenschappen/UMCG, 2013, NARCIS

URL: https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; 3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; 11370/3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; urn:isbn:9789036764308 ; urn:isbn:9789036764292 ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html

► Dystrofische epidermolysis bullosa (DEB) is een erfelijke huidaandoening, veroorzaakt door mutaties in het COL7A1 gen. Bij DEB ontstaan reeds door geringe wrijving blaren van de… (more)

Subjects/Keywords: Proefschriften (vorm); Somatic mutations; Populatiegenetica; Databanken; Fenotype; Genotype; Dystrofie; Epidermolysis bullosa; aangeboren afwijkingen; dermatologie (geneeskunde)

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APA (6^th Edition):

Akker, P. C. v. d. (2013). Dystrophic epidermolysis bullosa: novel insights into the genotype-phenotype correlation and somatic mosaicism. (Doctoral Dissertation). NARCIS. Retrieved from https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; 3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; 11370/3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; urn:isbn:9789036764308 ; urn:isbn:9789036764292 ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html

Chicago Manual of Style (16^th Edition):

Akker, Peter Christiaan van den. “Dystrophic epidermolysis bullosa: novel insights into the genotype-phenotype correlation and somatic mosaicism.” 2013. Doctoral Dissertation, NARCIS. Accessed January 22, 2021. https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; 3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; 11370/3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; urn:isbn:9789036764308 ; urn:isbn:9789036764292 ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html.

MLA Handbook (7^th Edition):

Akker, Peter Christiaan van den. “Dystrophic epidermolysis bullosa: novel insights into the genotype-phenotype correlation and somatic mosaicism.” 2013. Web. 22 Jan 2021.

Vancouver:

Akker PCvd. Dystrophic epidermolysis bullosa: novel insights into the genotype-phenotype correlation and somatic mosaicism. [Internet] [Doctoral dissertation]. NARCIS; 2013. [cited 2021 Jan 22]. Available from: https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; 3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; 11370/3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; urn:isbn:9789036764308 ; urn:isbn:9789036764292 ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html.

Council of Science Editors:

Akker PCvd. Dystrophic epidermolysis bullosa: novel insights into the genotype-phenotype correlation and somatic mosaicism. [Doctoral Dissertation]. NARCIS; 2013. Available from: https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; 3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; 11370/3acb2fda-cd7d-4bc4-9b9b-eec911c20d37 ; urn:isbn:9789036764308 ; urn:isbn:9789036764292 ; urn:nbn:nl:ui:11-dbi/525e96a7b771a ; https://www.rug.nl/research/portal/en/publications/dystrophic-epidermolysis-bullosa(3acb2fda-cd7d-4bc4-9b9b-eec911c20d37).html

27. Sawai, Yugo. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations .

Degree: 2016, Kyoto University

URL: http://hdl.handle.net/2433/215393

Subjects/Keywords: Activation-induced cytidine deaminase; Pancreatic cancer; Acinar-ductal metaplasia; Pancreatic intraepithelial neoplasia; Somatic mutations

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APA (6^th Edition):

Sawai, Y. (2016). Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/215393

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sawai, Yugo. “Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations .” 2016. Thesis, Kyoto University. Accessed January 22, 2021. http://hdl.handle.net/2433/215393.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sawai, Yugo. “Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations .” 2016. Web. 22 Jan 2021.

Vancouver:

Sawai Y. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations . [Internet] [Thesis]. Kyoto University; 2016. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/2433/215393.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sawai Y. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations . [Thesis]. Kyoto University; 2016. Available from: http://hdl.handle.net/2433/215393

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. Youssef, Sarah Hisham Abdelaziz. Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia.

Degree: MS, Pharmaceutical Sciences, 2018, University of Tennessee Health Science Center

URL: https://dc.uthsc.edu/dissertations/458

► Despite the improved outcome associated with current treatment strategies ofpediatric acute lymphoblastic leukemia (ALL), relapse still represents a major challenge. Pediatric ALL demonstrates branched… (more)

Subjects/Keywords: Acute Lymphoblastic Leukemia; Circulating-tumor DNA (Ct-DNA); Clonal Dynamics; Leukemia-derived Circulating DNA; Pediatrics; Somatic Mutations; Medical Genetics; Medical Molecular Biology; Medical Sciences; Medicine and Health Sciences; Pharmacy and Pharmaceutical Sciences

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APA (6^th Edition):

Youssef, S. H. A. (2018). Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia. (Thesis). University of Tennessee Health Science Center. Retrieved from https://dc.uthsc.edu/dissertations/458

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Youssef, Sarah Hisham Abdelaziz. “Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia.” 2018. Thesis, University of Tennessee Health Science Center. Accessed January 22, 2021. https://dc.uthsc.edu/dissertations/458.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Youssef, Sarah Hisham Abdelaziz. “Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia.” 2018. Web. 22 Jan 2021.

Vancouver:

Youssef SHA. Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia. [Internet] [Thesis]. University of Tennessee Health Science Center; 2018. [cited 2021 Jan 22]. Available from: https://dc.uthsc.edu/dissertations/458.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Youssef SHA. Somatic Mutation Detection in Leukemia-Derived Circulating DNA: Utility in Monitoring Clonal Dynamics and Disease Response in Pediatric Acute Lymphoblastic Leukemia. [Thesis]. University of Tennessee Health Science Center; 2018. Available from: https://dc.uthsc.edu/dissertations/458

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

29. Θώμου, Χριστίνα. Επίκτητες σωματικές μεταλλάξεις στο μικροδορυφορικό DNA σε παιδιά με βρογχικό άσθμα.

Degree: 2010, University of Crete (UOC); Πανεπιστήμιο Κρήτης

URL: http://hdl.handle.net/10442/hedi/24661

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Objectives High incidence of genetic alterations at the microsatellite (MS) DNA level has been reported in asthmatic adults. Working Hypothesis The aim of this study… (more)

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Objectives High incidence of genetic alterations at the microsatellite (MS) DNA level has been reported in asthmatic adults. Working Hypothesis The aim of this study was to investigate whether microsatellite instability (MSI) and loss of heterozygosity (LOH) were detectable phenomena in children with asthma. Methodology DNA was extracted from sputum and blood cells of 27 children (10.8 ± 2.5 years) with mild to moderate asthma, and from 8 healthy, never-smoked young adults. Fourteen polymorphic MS markers, namely D5S207, D5S820, D5S637, D6S344, D6S2223, D6S263, SGC35231, D11S1253, D11S1337, D11S97, USAT24G1, D13S273, D14S258, and D14S292, located on chromosomes (chr) 5q, 6p, 11q, 13q, and 14q were used to assess MSI and LOH. Results None of the healthy subjects exhibited any genetic alteration. Five out of 27 children (18.5%) exhibited MSI or LOH in sputum cells versus blood samples from which 3 in the marker USAT24G1 (chr 13q14.1), 1 in the marker D14S258 (chr 14q23-q24.3), and 1 in the marker D5S637 (chr 5q12-q13). Compared to a previous study, with asthmatic adults, whereas MSI and/or LOH was exhibited in approximately 60% of the cases, the current study reported <20% of genetic alterations, at the MS DNA, in asthmatic children. Conclusions Our results showed that genetic instability in the MS DNA, is present in asthmatic children, but to less extent than in adult asthmatics from previous studies. These findings may support the hypothesis that somatic mutations may be early acquired in the natural course of asthma and could represent another contributor to the molecular pathogenesis of the disease. However, further studies are needed to clarify this hypothesis.

Σκοπός Υψηλή επίπτωση γενετικών αλλαγών σε επίπεδο μικροδορυφορικού (ΜΔ) DNA έχει καταγραφεί σε ενήλικες με άσθμα. Υπόθεση Σκοπός αυτής της μελέτης ήταν να ερευνήσει εάν η μικροδορυφορική αστάθεια (ΜΔΑ) και η απώλεια της ετεροζυγωτίας (ΑΤΕ) είναι ανιχνεύσιμα φαινόμενα σε παιδιά με άσθμα. Μεθοδολογία Έγινε εκχύλιση DNA από κύτταρα πτυέλων και αίματος σε 27 παιδιά (10,8 ± 2,5 έτη) με ήπιο έως μέτριο άσθμα, και από 8 υγιείς, μη καπνιστές, νέους ενήλικες. Χρησιμοποιήθηκαν οι κάτωθι 14 πολυμορφικοί ΜΔ δείκτες: D5S207, D5S820, D5S637, D6S344, D6S2223, D6S263, SGC35231, D11S1253, D11S1337, D11S97, USAT24G1, D13S273, D14S258 και D14S292, οι οποίοι εντοπίζονται στα χρωμοσώματα (χρ) 5q, 6p, 11q, 13q και 14q, με σκοπό να εκτιμηθεί η ΜΔΑ και η ΑΤΕ. Αποτελέσματα Κανένας από τους υγιείς ενήλικες δεν παρουσίασε κάποια γενετική αλλαγή. Πέντε από τα 27 παιδιά (18,5%) παρουσίασαν ΜΔΑ ή ΑΤΕ στα κύτταρα πτυέλου έναντι των δειγμάτων αίματος εκ των οποίων 3 στο δείκτη USAT24G1 (χρ 13q14.1), 1 στο δείκτη D14S258 (χρ 14q23-q24.3) και 1 στο δείκτη D5S637 (χρ 5q12-q13). Συγκριτικά με προηγούμενη μελέτη σε ασθματικούς ενήλικες, όπου ΜΔΑ και/ή ΑΤΕ παρουσιάστηκε στο 60% περίπου των περιστατικών, στην παρούσα μελέτη καταγράφηκαν γενετικές αλλαγές στο ΜΔ DNA σε <20% των ασθματικών παιδιών. Συμπεράσματα Τα αποτελέσματά μας έδειξαν ότι η γενετική αστάθεια στο ΜΔ DNA είναι παρούσα σε…

Subjects/Keywords: Παιδικό άσθμα; Γενετική ευαισθησία; Μικροδορυφορική αστάθεια; Απώλεια της ετεροζυγωτίας; Προκλητά πτύελα; Σωματικές μεταλλάξεις; Childhood asthma; Genetic susceptibility; Microsatellite instability ( MSI ); Loss of heterozygosity; Induced sputum; Somatic mutations

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Θώμου, . �. (2010). Επίκτητες σωματικές μεταλλάξεις στο μικροδορυφορικό DNA σε παιδιά με βρογχικό άσθμα. (Thesis). University of Crete (UOC); Πανεπιστήμιο Κρήτης. Retrieved from http://hdl.handle.net/10442/hedi/24661

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Θώμου, Χριστίνα. “Επίκτητες σωματικές μεταλλάξεις στο μικροδορυφορικό DNA σε παιδιά με βρογχικό άσθμα.” 2010. Thesis, University of Crete (UOC); Πανεπιστήμιο Κρήτης. Accessed January 22, 2021. http://hdl.handle.net/10442/hedi/24661.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Θώμου, Χριστίνα. “Επίκτητες σωματικές μεταλλάξεις στο μικροδορυφορικό DNA σε παιδιά με βρογχικό άσθμα.” 2010. Web. 22 Jan 2021.

Vancouver:

Θώμου �. Επίκτητες σωματικές μεταλλάξεις στο μικροδορυφορικό DNA σε παιδιά με βρογχικό άσθμα. [Internet] [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2010. [cited 2021 Jan 22]. Available from: http://hdl.handle.net/10442/hedi/24661.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Θώμου �. Επίκτητες σωματικές μεταλλάξεις στο μικροδορυφορικό DNA σε παιδιά με βρογχικό άσθμα. [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2010. Available from: http://hdl.handle.net/10442/hedi/24661

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Uijtewaal, B.A. The production and evaluation of monohaploid potatoes (2n=x=12) for breeding research on cell and plant level.

Degree: 1987, Agricultural University

URL: http://library.wur.nl/WebQuery/wurpubs/3806 ; urn:nbn:nl:ui:32-3806 ; urn:nbn:nl:ui:32-3806 ; http://library.wur.nl/WebQuery/wurpubs/3806

► The use of monohaploid potato clones in research in theory has many potential advantages in comparison with the use of heterozygous di- and tetraploids.… (more)

▼ The use of monohaploid potato clones in research in theory has many potential advantages in comparison with the use of heterozygous di- and tetraploids. Because in monohaploids each chromosome is single, recessive as well as dominant alleles are detectable and can be selected for. In addition, monohaploids offer a unique opportunity to produce homozygous clones. The aim of the study presented in this thesis was to determine which are the pros and cons of using monohaploids in practical breeding and fundamental research, and which are the consequences of monoploidy and homozygosity in a normally highly heterozygous crop such as potato. Large-scale production of monohaploids appeared to be possible by prickle pollination, but turned out to be genotype-specific. It was shown that the ability for monohaploid production can be transferred to the progeny by crossing. During the investigation reported herein more than 500 monohaploids have been produced that could be used for further research. In order to combine different selected monohaploid genotypes that will warrant high-level heterozygosity, methods for protoplast isolation, culture and fusion have been adjusted to the material used. Several monohaploid genotypes could be regenerated from protoplasts to plants but always the ploidy level raised to 2x or even 4x. After protoplast fusion, hybrid fusion products could readily be selected because of a differential regeneration capacity. By using isozyme markers for detection of hybridity the first regenerants after protoplast fusion were shown to be hybrids. A difference of at least four weeks in regeneration time was found between the first heterozygous (hybrids) and the first homozygous (parental) genotypes. Some regenerants were triploid. This indicates that at least one monohaploid protoplast was involved in fusion. The majority however was tetraploid and this was probably the result of somatically doubling x+x fusion products. Only in some genotype combinations also increased callus growth rates were found. The plant vigour in homo- and heterozygotes suggests that dominance effects are stronger than additive gene effects. Owing to sterility problems and a relatively bad plant performance, homozygous and there fore also indirectly monohaploid potato clones are of little importance for practical breeding. However, for fundamental research, monohaploids are very useful: (i) they can be produced on a large scale from specific diploid lines, (ii) they can be maintained in vitro on the monohaploid level for at least 2-3 years via shoot tip propagation, and (iii) protoplast isolation and fusion, and plant regeneration from protoplast derived calli has proven to be possible. Advisors/Committee Members: J.G.T. Hermsen, E. Jacobsen.

Subjects/Keywords: genomen; haploïdie; hybriden; soortkruising; mutaties; plantenveredeling; polyploïdie; aardappelen; solanum tuberosum; somatische hybridisatie; Plantenveredeling, selectiemethoden; genomes; haploidy; hybrids; interspecific hybridization; mutations; plant breeding; polyploidy; potatoes; solanum tuberosum; somatic hybridization; Plant Breeding and Selection Methods

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Uijtewaal, B. A. (1987). The production and evaluation of monohaploid potatoes (2n=x=12) for breeding research on cell and plant level. (Doctoral Dissertation). Agricultural University. Retrieved from http://library.wur.nl/WebQuery/wurpubs/3806 ; urn:nbn:nl:ui:32-3806 ; urn:nbn:nl:ui:32-3806 ; http://library.wur.nl/WebQuery/wurpubs/3806

Chicago Manual of Style (16^th Edition):

Uijtewaal, B A. “The production and evaluation of monohaploid potatoes (2n=x=12) for breeding research on cell and plant level.” 1987. Doctoral Dissertation, Agricultural University. Accessed January 22, 2021. http://library.wur.nl/WebQuery/wurpubs/3806 ; urn:nbn:nl:ui:32-3806 ; urn:nbn:nl:ui:32-3806 ; http://library.wur.nl/WebQuery/wurpubs/3806.

MLA Handbook (7^th Edition):

Uijtewaal, B A. “The production and evaluation of monohaploid potatoes (2n=x=12) for breeding research on cell and plant level.” 1987. Web. 22 Jan 2021.

Vancouver:

Uijtewaal BA. The production and evaluation of monohaploid potatoes (2n=x=12) for breeding research on cell and plant level. [Internet] [Doctoral dissertation]. Agricultural University; 1987. [cited 2021 Jan 22]. Available from: http://library.wur.nl/WebQuery/wurpubs/3806 ; urn:nbn:nl:ui:32-3806 ; urn:nbn:nl:ui:32-3806 ; http://library.wur.nl/WebQuery/wurpubs/3806.

Council of Science Editors:

Uijtewaal BA. The production and evaluation of monohaploid potatoes (2n=x=12) for breeding research on cell and plant level. [Doctoral Dissertation]. Agricultural University; 1987. Available from: http://library.wur.nl/WebQuery/wurpubs/3806 ; urn:nbn:nl:ui:32-3806 ; urn:nbn:nl:ui:32-3806 ; http://library.wur.nl/WebQuery/wurpubs/3806

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