BMC Cancer Research article Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors Michael A Kiebish and Thomas N Seyfried* BioMed Central Open Access Address: Department of Biology, Boston College, Chestnut Hill, MA 02467 USA Email: Michael A Kiebish - Kiebish@bc.edu; Thomas N Seyfried* - Thomas.Seyfried@bc.edu * Corresponding author Published: 16 August 2005 BMC Cancer 2005, 5:102 doi:10.1186/1471-2407-5-102 This article is available from: http://www.biomedcentral.com/1471-2407/5/102 Received: 19 May 2005 Accepted: 16 August 2005 © 2005 Kiebish and Seyfried; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Somatic mutations in the mitochondrial genome occur in numerous tumor types including brain tumors. These mutations are generally found in the hypervariable regions I and II of the displacement loop and unlikely alter mitochondrial function. Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (OL) and the Arg tRNA. Methods: In this study we examined the entire mitochondrial genome in a series of chemically induced brain tumors in the C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. The tumor mtDNA was compared to that of mtDNA in brain mitochondrial populations from the corresponding syngeneic mouse host strain. Results: Direct sequencing revealed a few homoplasmic base pair insertions, deletions, and substitutions in the tumor cells mainly in regions of mononucleotide repeats. A heteroplasmic mutation in the 16srRNA gene was detected in a spontaneous metastatic VM brain tumor. Conclusion: None of the mutations were considered pathogenic, indicating that mtDNA somatic mutations do not likely contribute to the initiation or progression of these diverse mouse brain tumors. Background Mitochondrial DNA (mtDNA) is essential for the produc- tion of subunits for the electron transport chain, since it encodes peptides for Complex I, III, IV, and V. The mito- chondrial genome consists of a 16.5 kb piece of circular DNA encoding 37 genes on the L and H strands. These include 22 tRNAs, 2 rRNAs, and 13 respiratory chain sub- units [1]. The mitochondrial genetic code varies slightly from the nuclear genetic code and the mutation rate of the mitochondrial genome is 10 fold higher than that of the nuclear genome [2-4]. This higher mutation rate may be due in part to a lack of protective histones, reduced fidelity of polymerase γ, or to the localization of the mitochon- drial genome to the inner mitochondrial membrane near damaging reactive oxygen species [5-9]. mtDNA muta- tions may also contribute to a decrease in metabolic effi- ciency that enhances aging, promotes neurodegeneration, and is conducive to carcinogenesis [10-12]. mtDNA mutations have been studied in various types of cancers, including breast [13], bladder, lung, head and neck [14], gastric [15], esophageal [16], pancreatic [17], and colon [18]. The majority of the mutations in the mito- chondrial genome of human tumors were found in the Page 1 of 8 (page number not for citation purposes)