Comprehensive molecular characterization of mitochondrial genomes in human cancers
Authors
Wang, Yumeng
Yoon, Christopher J.
Yang, Yang
Martincorena, Inigo
Xu, Yanxun
Kim, Hyung-Lae
Nakagawa, Hidewaki
Publication Date
2020-02-05Journal Title
Nature Genetics
ISSN
1061-4036
Publisher
Nature Publishing Group US
Volume
52
Issue
3
Pages
342-352
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Yuan, Y., Ju, Y. S., Kim, Y., Li, J., Wang, Y., Yoon, C. J., Yang, Y., et al. (2020). Comprehensive molecular characterization of mitochondrial genomes in human cancers. Nature Genetics, 52 (3), 342-352. https://doi.org/10.1038/s41588-019-0557-x
Abstract
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.
Keywords
Analysis, /631/67, /631/208/212, /45/23, analysis
Identifiers
s41588-019-0557-x, 557
External DOI: https://doi.org/10.1038/s41588-019-0557-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317151
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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