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  -