Comprehensive molecular characterization of mitochondrial genomes in human cancers
Top Cited Papers
Open Access
- 29 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 52 (3), 342-+
- https://doi.org/10.1038/s41588-019-0557-x
Abstract
Mitochondria are essential cellular organelles that play critical roles in cancer. Here, as part of the International Cancer Genome Consortium/The Cancer Genome Atlas Pan-Cancer Analysis of Whole Genomes Consortium, which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we performed a multidimensional, integrated characterization of mitochondrial genomes and related RNA sequencing data. Our analysis presents the most definitive mutational landscape of mitochondrial genomes and identifies several hypermutated cases. Truncating mutations are markedly enriched in kidney, colorectal and thyroid cancers, suggesting oncogenic effects with the activation of signaling pathways. We find frequent somatic nuclear transfers of mitochondrial DNA, some of which disrupt therapeutic target genes. Mitochondrial copy number varies greatly within and across cancers and correlates with clinical variables. Co-expression analysis highlights the function of mitochondrial genes in oxidative phosphorylation, DNA repair and the cell cycle, and shows their connections with clinically actionable genes. Our study lays a foundation for translating mitochondrial biology into clinical applications. Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.This publication has 54 references indexed in Scilit:
- The Cancer Genome Atlas Pan-Cancer analysis projectNature Genetics, 2013
- Integrated genomic characterization of endometrial carcinomaNature, 2013
- Human mitochondrial DNA: roles of inherited and somatic mutationsNature Reviews Genetics, 2012
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- Mutational Processes Molding the Genomes of 21 Breast CancersCell, 2012
- The Human Mitochondrial TranscriptomeCell, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Allele-specific copy number analysis of tumorsProceedings of the National Academy of Sciences of the United States of America, 2010
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- BLAT—The BLAST-Like Alignment ToolGenome Research, 2002