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).