Comprehensive molecular characterization of mitochondrial genomes in human cancers

PCAWG Consortium

Research output: Contribution to journalArticlepeer-review

220 Scopus citations


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.

Original languageEnglish
Pages (from-to)342-352
Number of pages11
JournalNature Genetics
Issue number3
StatePublished - 1 Mar 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).


This study was partially supported by an MD Anderson Cancer Center Faculty Scholar Award (to H.L.), the Lorraine Dell Program in Bioinformatics for Personalization of Cancer Medicine (to J.N.W.), an Institute for Information and Communications Technology Promotion grant funded by the Korean government (Ministry of Science, ICT and Future Planning) (B0101-15-0104; the development of a supercomputing system for genome analysis), the Korea Health Technology Research and Development Project (through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea) (HI14C0072 to H.-L.K. and HI17C1836 to Y.S.J.) and the Korean National Research Foundation (NRF-2016R1D1A1B03934110 and NRF-2017R1A2B2012796). We also thank the Electronics and Telecommunications Research Institute in Korea for its commitment to the ICGC PCAWG projects, the MD Anderson Cancer Center High-Performance Computing Core Facility for computing, and L. Chastain for editorial assistance. We acknowledge the contributions of the members of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonized variant calling of the cancer genomes used in this study. We thank the patients and their families for participation in the individual ICGC and TCGA projects.

FundersFunder number
Korea Health Technology Research and Development Project
Korean National Research FoundationNRF-2016R1D1A1B03934110, NRF-2017R1A2B2012796
Lorraine Dell Program
National Cancer InstituteP30CA016672
University of Texas MD Anderson Cancer Center
Ministry of Science, ICT and Future PlanningB0101-15-0104
Ministry of Health and WelfareHI14C0072, HI17C1836
Korea Health Industry Development Institute
Institute for Information and Communications Technology Promotion


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