Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors.
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.


CONCLUSIONS
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.
Kiebish
Michael A
MA
Department of Biology, Boston College, Chestnut Hill, MA 02467, USA. Kiebish@bc.edu
Seyfried
Thomas N
TN
D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D017353:Gene Deletion; D016678:Genome; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012336:RNA, Ribosomal, 16S / Q000378:metabolism
D017931:DNA Primers; D004272:DNA, Mitochondrial; D012336:RNA, Ribosomal, 16S