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You searched for subject:(Driver mutation). Showing records 1 – 2 of 2 total matches.

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Washington University in St. Louis

1. Xie, Mingchao. Discovery and Functional Implication of Genetic Alterations Associated with Clonal Hematopoietic Expansion.

Degree: PhD, Biology & Biomedical Sciences (Computational & Systems Biology), 2016, Washington University in St. Louis

Cancers, including hematologic malignancies, arise as a result of the stepwise accumulation of mutations. Some early mutations that potentially initiate clonal expansion might exist in patients many years before they develop obvious disease symptoms. Therefore, identifying and characterizing these early mutations are critical to understanding the genetic basis of tumorigenesis. Here, we analyzed blood-derived DNA sequencing data from 2,728 individuals without apparent hematologic malignancies and identified 77 blood-specific mutations in 31 cancer-associated genes. Importantly, 83% of all mutations occurred in 19 genes that have been previously linked to hematological malignancies, such as DNMT3A, TET2, JAK2, and ASXL1. By investigating these mutations in different hematologic diseases, we identified several recurrently mutated genes that may be disease initiators. To obtain more comprehensive profiling of genes and variants associated with clonal hematopoietic expansion, we processed an additional 3,221 normal blood samples from The Cancer Genome Atlas (TCGA) and developed a statistical approach to systematically identify blood-specific mutations in all human genes. 26 genes were significantly mutated in human blood samples, including PPM1D. Functional validation showed that PPM1D mutations suppressed the phosphorylation of TP53 at Ser15, suggesting that the blood-specific mutants in PPM1D retain its phosphatase activity in regulating TP53. We also characterized rare copy number variations (CNVs) in blood samples and discovered about half of the individuals examined carried rare somatic CNVs in their blood. Some of these CNVs were associated with genes involved in hematological malignancies, such as JAK2, ASXL1, and FLT3. In summary, we systematically identified early genomic alterations in normal blood cells by utilizing the large-scale sequencing data and further determined the functional impact of the mutations in the recurrently mutated gene. Our comprehensive analysis of blood-specific genomic alterations will shed light on understanding the complex mechanisms of hematologic malignancies and also facilitate the development of more efficient strategies for early detection, prevention, and treatment of hematologic cancer. Advisors/Committee Members: Li Ding, Barak A. Cohen, Todd E. Druley, John R. Edwards, Daniel C. Link.

Subjects/Keywords: Age; Blood somatic mutation; Clonal expansion; Initial driver mutation; PPM1D; TP53

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

APA (6th Edition):

Xie, M. (2016). Discovery and Functional Implication of Genetic Alterations Associated with Clonal Hematopoietic Expansion. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/art_sci_etds/1015

Chicago Manual of Style (16th Edition):

Xie, Mingchao. “Discovery and Functional Implication of Genetic Alterations Associated with Clonal Hematopoietic Expansion.” 2016. Doctoral Dissertation, Washington University in St. Louis. Accessed November 19, 2019. https://openscholarship.wustl.edu/art_sci_etds/1015.

MLA Handbook (7th Edition):

Xie, Mingchao. “Discovery and Functional Implication of Genetic Alterations Associated with Clonal Hematopoietic Expansion.” 2016. Web. 19 Nov 2019.

Vancouver:

Xie M. Discovery and Functional Implication of Genetic Alterations Associated with Clonal Hematopoietic Expansion. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2016. [cited 2019 Nov 19]. Available from: https://openscholarship.wustl.edu/art_sci_etds/1015.

Council of Science Editors:

Xie M. Discovery and Functional Implication of Genetic Alterations Associated with Clonal Hematopoietic Expansion. [Doctoral Dissertation]. Washington University in St. Louis; 2016. Available from: https://openscholarship.wustl.edu/art_sci_etds/1015

2. Díaz-Uriarte, Ramón. Identifying restrictions in the order of accumulation of mutations during tumor progression: Effects of passengers, evolutionary models, and sampling.

Degree: 2018, BioMed Central

Subjects/Keywords: Conjunctive bayesian network; Driver mutation; Oncogenetic tree; Passenger mutation; Tumor evolution; Tumor progression model; Medicina

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

APA (6th Edition):

Díaz-Uriarte, R. (2018). Identifying restrictions in the order of accumulation of mutations during tumor progression: Effects of passengers, evolutionary models, and sampling. (Thesis). BioMed Central. Retrieved from http://hdl.handle.net/10486/669519

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

Chicago Manual of Style (16th Edition):

Díaz-Uriarte, Ramón. “Identifying restrictions in the order of accumulation of mutations during tumor progression: Effects of passengers, evolutionary models, and sampling.” 2018. Thesis, BioMed Central. Accessed November 19, 2019. http://hdl.handle.net/10486/669519.

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

MLA Handbook (7th Edition):

Díaz-Uriarte, Ramón. “Identifying restrictions in the order of accumulation of mutations during tumor progression: Effects of passengers, evolutionary models, and sampling.” 2018. Web. 19 Nov 2019.

Vancouver:

Díaz-Uriarte R. Identifying restrictions in the order of accumulation of mutations during tumor progression: Effects of passengers, evolutionary models, and sampling. [Internet] [Thesis]. BioMed Central; 2018. [cited 2019 Nov 19]. Available from: http://hdl.handle.net/10486/669519.

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

Council of Science Editors:

Díaz-Uriarte R. Identifying restrictions in the order of accumulation of mutations during tumor progression: Effects of passengers, evolutionary models, and sampling. [Thesis]. BioMed Central; 2018. Available from: http://hdl.handle.net/10486/669519

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

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