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Comprehensive molecular characterization of mitochondrial genomes in human cancers

Yuan, Yuan ; Ju, Young Seok ; Kim, Youngwook ; Li, Jun ; Wang, Yumeng ; Yoon, Christopher J ; Yang, Yang ; Martincorena, Inigo ; Creighton, Chad J and Weinstein, John N , et al. (2020) In Nature Genetics 52(3). p.342-352
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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Cell Cycle/genetics, DNA Copy Number Variations, DNA Repair/genetics, DNA, Mitochondrial/genetics, Genome, Human/genetics, Genome, Mitochondrial/genetics, Humans, Mutation, Neoplasms/genetics, Oxidative Phosphorylation, Sequence Analysis, RNA, Whole Genome Sequencing
in
Nature Genetics
volume
52
issue
3
pages
342 - 352
publisher
Nature Publishing Group
external identifiers
  • scopus:85079059405
  • pmid:32024997
ISSN
1546-1718
DOI
10.1038/s41588-019-0557-x
language
English
LU publication?
yes
id
8f1c62ab-fa08-4872-abf2-d33f162c1225
date added to LUP
2023-03-29 17:21:41
date last changed
2024-04-18 20:29:05
@article{8f1c62ab-fa08-4872-abf2-d33f162c1225,
  abstract     = {{<p>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.</p>}},
  author       = {{Yuan, Yuan and Ju, Young Seok and Kim, Youngwook and Li, Jun and Wang, Yumeng and Yoon, Christopher J and Yang, Yang and Martincorena, Inigo and Creighton, Chad J and Weinstein, John N and Xu, Yanxun and Han, Leng and Kim, Hyung-Lae and Nakagawa, Hidewaki and Park, Keunchil and Campbell, Peter J and Liang, Han}},
  issn         = {{1546-1718}},
  keywords     = {{Cell Cycle/genetics; DNA Copy Number Variations; DNA Repair/genetics; DNA, Mitochondrial/genetics; Genome, Human/genetics; Genome, Mitochondrial/genetics; Humans; Mutation; Neoplasms/genetics; Oxidative Phosphorylation; Sequence Analysis, RNA; Whole Genome Sequencing}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{342--352}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Comprehensive molecular characterization of mitochondrial genomes in human cancers}},
  url          = {{http://dx.doi.org/10.1038/s41588-019-0557-x}},
  doi          = {{10.1038/s41588-019-0557-x}},
  volume       = {{52}},
  year         = {{2020}},
}