Heteroplasmic shifts in tumor mitochondrial genomes reveal tissue-specific signals of relaxed and positive selection.

ABSTRACT: Although mitochondrial genomes (mtDNA) accumulate elevated levels of mutations in cancer cells, the origin and functional impact of these mutations remain controversial. Here, we queried whole-genome sequence data from 1,916 patients across 24 cancer types to characterize patterns of mtDNA mutations and elucidate the selective constraints driving their fate. Given that mitochondrial genomes are polyploid, cells with advantageous levels of mtDNA mutations can be selected for depending on their cellular environment. Therefore, we tracked changes in per-cell abundances of mtDNA mutations from normal to tumor cells in the same patient. Tumor mitochondrial genomes show distinct mutational patterns and are disproportionately enriched for protein-altering changes. Moreover, protein-altering mtDNA

SUBMITTER: Grandhi S 

PROVIDER: S-EPMC5886292 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature