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Reference: Ju, YS, Alexandrov, LB, Gerstung, M et al., (2014). Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer. eLife, 3 (October), Article: e02935.Citable link to this page:

 

Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer

Abstract: Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's versionNotes:This is an open-access article,free of all copyright, and may befreely reproduced, distributed,transmitted, modified, builtupon, or otherwise used byanyone for any lawful purpose.The work is made available underthe Creative Commons CC0public domain dedication.

Bibliographic Details

Publisher: eLife Sciences Publications

Publisher Website: http://elife.elifesciences.org/

Journal: eLifesee more from them

Publication Website: http://www.elifesciences.org/

Issue Date: 2014-1

pages:Article: e02935Identifiers

Urn: uuid:1b9f6656-1bba-4bb7-8fdd-68bbb78ea1e2

Source identifier: 485988

Eissn: 2050-084X

Doi: https://doi.org/10.7554/elife.02935

Issn: 2050-084X Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: ICGC Breast Cancer Group ICGC Chronic Myeloid Disorders Group ICGC Prostate Cancer Group Animals Humans Mitochondria DNA DNA, Mitochondrial DNA, Neoplasm Evolution, Molecular Mutation DNA Replication Data Mining Genome, Mitochondrial Base Composition Neoplasms Polymorphism, Single Nucleotide High-Throughput Nucleotide Sequencing Tiny URL: pubs:485988

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Autor: Ju, YS - - - Alexandrov, LB - - - Gerstung, M - - - Martincorena, I - - - Nik-Zainal, S - - - Ramakrishna, M - - - Davies, HR - -

Fuente: https://ora.ox.ac.uk/objects/uuid:1b9f6656-1bba-4bb7-8fdd-68bbb78ea1e2



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