Comprehensive molecular characterization of mitochondrial genomes in human cancers
(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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- author
- contributor
- Borg, Åke LU ; Ringnér, Markus LU and Staaf, Johan LU
- author collaboration
- organization
- publishing date
- 2020-03
- 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
- 2024-06-29 04:48:46
@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}}, }