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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 ; Weinstein, John N ; Xu, Yanxun ; Han, Leng ; Kim, Hyung-Lae ; Nakagawa, Hidewaki ; Park, Keunchil ; Campbell, Peter J ; Liang, Han

Nature genetics, 2020-03, Vol.52 (3), p.342-352 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Comprehensive molecular characterization of mitochondrial genomes in human cancers
Autor: Yuan, Yuan ; Ju, Young Seok ; Kim, Youngwook ; Li, Jun ; Wang, Yumeng ; Yoon, Christopher J ; Yang, Yang ; Martincorena, Inigo ; Creighton, Chad J ; Weinstein, John N ; Xu, Yanxun ; Han, Leng ; Kim, Hyung-Lae ; Nakagawa, Hidewaki ; Park, Keunchil ; Campbell, Peter J ; Liang, Han
Assuntos: Age ; Analysis ; Basic Medicine ; Cancer ; Cell cycle ; Cell Cycle - genetics ; Consortia ; Copy number ; Correlation analysis ; Deoxyribonucleic acid ; DNA ; DNA Copy Number Variations ; DNA damage ; DNA repair ; DNA Repair - genetics ; DNA, Mitochondrial - genetics ; Gene expression ; Gene sequencing ; Genes ; Genetic aspects ; Genetic research ; Genome, Human - genetics ; Genome, Mitochondrial - genetics ; Genomes ; Health aspects ; Humans ; Mathematical analysis ; Medical and Health Sciences ; Medical Genetics ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Mitochondria ; Mitochondrial DNA ; Mutation ; Neoplasms - genetics ; Oncology, Experimental ; Organelles ; Oxidative Phosphorylation ; Phosphorylation ; Ribonucleic acid ; RNA ; Sequence Analysis, RNA ; Signatures ; Therapeutic applications ; Thyroid ; Thyroid gland ; Transfer RNA ; Whole Genome Sequencing
É parte de: Nature genetics, 2020-03, Vol.52 (3), p.342-352
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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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 ; Weinstein, John N ; Xu, Yanxun ; Han, Leng ; Kim, Hyung-Lae ; Nakagawa, Hidewaki ; Park, Keunchil ; Campbell, Peter J ; Liang, Han

United States: Nature Publishing Group

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