Spectrum of somatic mitochondrial mutations in five cancers

Larman T.C.; DePalma S.R.; Hadjipanayis A.G.Protopopov A.Zhang J.Gabriel S.B.Chin L.Seidman C.E.Kucherlapati R.Seidman J.G.

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Spectrum of somatic mitochondrial mutations in five cancers

机译：Spectrum of somatic mitochondrial mutations in five cancers

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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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第35期|14087-14091|共5页
作者
Larman T.C.; DePalma S.R.; Hadjipanayis A.G.Protopopov A.Zhang J.Gabriel S.B.Chin L.Seidman C.E.Kucherlapati R.Seidman J.G.;
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作者单位

Department of Genetics, Harvard Medical School, Boston, MA 02115, United States;

Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, United States;

Broad Institute, Cambridge, MA 02142, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Acute myeloid leukemia; Colon adenocarcinoma; Deleterious mutations; Ovarian serous cystadenocarcinoma; Rectal adenomcarcinoma;

Spectrum of somatic mitochondrial mutations in five cancers

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