TY - JOUR IS - 3 AV - public A1 - Yuan, Yuan A1 - Ju, Young Seok A1 - Kim, Youngwook A1 - Li, Jun A1 - Wang, Yumeng A1 - Yoon, Christopher J A1 - Yang, Yang A1 - Martincorena, Inigo A1 - Creighton, Chad J A1 - Weinstein, John N A1 - Xu, Yanxun A1 - Han, Leng A1 - Kim, Hyung-Lae A1 - Nakagawa, Hidewaki A1 - Park, Keunchil A1 - Campbell, Peter J A1 - Liang, Han N2 - 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. SP - 342 EP - 352 JF - Nature Genetics VL - 52 PB - Springer Science and Business Media LLC ID - discovery10148075 Y1 - 2020/03/02/ UR - https://doi.org/10.1038/s41588-019-0557-x TI - Comprehensive molecular characterization of mitochondrial genomes in human cancers N1 - © 2022 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). ER -