Comprehensive molecular characterization of mitochondrial genomes in human cancers

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dc.contributor.authorYuan, Yuanko
dc.contributor.authorJu, Young Seokko
dc.contributor.authorKim, Youngwookko
dc.contributor.authorLi, Junko
dc.contributor.authorWang, Yumengko
dc.contributor.authorYoon, Christopher J.ko
dc.contributor.authorYang, Yangko
dc.contributor.authorMartincorena, Inigoko
dc.contributor.authorCreighton, Chad J.ko
dc.contributor.authorWeinstein, John N.ko
dc.contributor.authorXu, Yanxunko
dc.contributor.authorHan, Lengko
dc.contributor.authorKim, Hyung-Laeko
dc.contributor.authorNakagawa, Hidewakiko
dc.contributor.authorPark, Keunchilko
dc.contributor.authorCampbell, Peter J.ko
dc.contributor.authorLiang, Hanko
dc.date.accessioned2020-07-30T02:55:07Z-
dc.date.available2020-07-30T02:55:07Z-
dc.date.created2020-02-26-
dc.date.created2020-02-26-
dc.date.created2020-02-26-
dc.date.issued2020-03-
dc.identifier.citationNATURE GENETICS, v.52, no.3, pp.342-
dc.identifier.issn1061-4036-
dc.identifier.urihttp://hdl.handle.net/10203/275673-
dc.description.abstractMitochondria 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. Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.titleComprehensive molecular characterization of mitochondrial genomes in human cancers-
dc.typeArticle-
dc.identifier.wosid000511282900005-
dc.identifier.scopusid2-s2.0-85079059405-
dc.type.rimsART-
dc.citation.volume52-
dc.citation.issue3-
dc.citation.beginningpage342-
dc.citation.publicationnameNATURE GENETICS-
dc.identifier.doi10.1038/s41588-019-0557-x-
dc.contributor.localauthorJu, Young Seok-
dc.contributor.nonIdAuthorYuan, Yuan-
dc.contributor.nonIdAuthorKim, Youngwook-
dc.contributor.nonIdAuthorLi, Jun-
dc.contributor.nonIdAuthorWang, Yumeng-
dc.contributor.nonIdAuthorYoon, Christopher J.-
dc.contributor.nonIdAuthorYang, Yang-
dc.contributor.nonIdAuthorMartincorena, Inigo-
dc.contributor.nonIdAuthorCreighton, Chad J.-
dc.contributor.nonIdAuthorWeinstein, John N.-
dc.contributor.nonIdAuthorXu, Yanxun-
dc.contributor.nonIdAuthorHan, Leng-
dc.contributor.nonIdAuthorKim, Hyung-Lae-
dc.contributor.nonIdAuthorNakagawa, Hidewaki-
dc.contributor.nonIdAuthorPark, Keunchil-
dc.contributor.nonIdAuthorCampbell, Peter J.-
dc.contributor.nonIdAuthorLiang, Han-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusDNA COPY NUMBER-
dc.subject.keywordPlusMUTATIONAL PROCESSES-
dc.subject.keywordPlusPOINT MUTATIONS-
dc.subject.keywordPlusLANDSCAPE-
dc.subject.keywordPlusTUMORS-
dc.subject.keywordPlusDAMAGE-
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