Spectrum of somatic mitochondrial mutations in five cancers

Tatianna C. Larman, Steven R. DePalma, Angela G. Hadjipanayis, Alexei Protopopov, Jianhua Zhang, Stacey B. Gabriel, Lynda Chin, Christine E. Seidman, Raju Kucherlapati, J. G. Seidman

Research output: Contribution to journalArticlepeer-review


Somatic mtDNA mutations have been reported in some human tumors, but their spectrum in different malignancies and their role in cancer development remain incompletely understood. Here, we describe the breadth of somatic and inherited mutations across the mitochondrial genome by sequence analyses of paired tumor and normal tissue samples from 226 individuals with five types of cancer using whole-genome data generated by The Cancer Genome Atlas Research Network. The frequencies of deleterious tumor-specific somatic mutations found in mtDNA varied across tumor types, ranging from 13% of glioblastomas to 63% of rectal adenocarcinomas. Comparedwith inheritedmtDNA variants, somatic mtDNA mutations were enriched for nonsynonymous vs. synonymous changes (93 vs. 15; P < 2.2E-16) and were predicted to functionally impact the encoded protein. Somatic missense mutations in tumors were distributed uniformly among the mitochondrial protein genes, but 65% of somatic truncating mutations occurred in NADH dehydrogenase 5. Analysis of staging data in colon and rectal cancers revealed that the frequency of damaging mitochondrial mutations is the same in stages I and IV tumors. In summary, these data suggest that damaging somatic mtDNA mutations occur frequently (13-63%) in these five tumor types and likely confer a selective advantage in oncogenesis.

Original languageEnglish (US)
Pages (from-to)14087-14091
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number35
StatePublished - Aug 28 2012
Externally publishedYes


  • Acute myeloid leukemia
  • Colon adenocarcinoma
  • Deleterious mutations
  • Ovarian serous cystadenocarcinoma
  • Rectal adenomcarcinoma

ASJC Scopus subject areas

  • General


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