Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from t...

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Autores: ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Demidov, German, 1990-, Drechsel, Oliver, Ossowski, Stephan, Estivill, Xavier, 1955-, Escaramís, Geòrgia, Bosio, Mattia, Holik, Aliaksei Z., Sušak, Hana, 1985-, Rabionet Janssen, Raquel, Stobbe, Miranda D., Marquès i Bonet, Tomàs, 1975-, Navarro i Cuartiellas, Arcadi, 1969-, Gut, Ivo Glynne, Beltran, Sergi, Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Heath, Simon, Prasad, Aparna, Heredia Genestar, José María, 1985-, Sabarinathan, Radhakrishnan, Pich Roselló, Oriol, 1992-, Gonzalez-Perez, Abel, Rubio Pérez, Carlota, 1990-, Tamborero Noguera, David, Mularoni, Loris, Deu-Pons, Jordi, Muiños, Ferran, Muyas Remolar, Francesc, 1992-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44263
Acceso en línea:http://hdl.handle.net/10230/44263
http://dx.doi.org/10.1038/s41586-020-1969-6
Access Level:acceso abierto
Palabra clave:Càncer
Genòmica
Genètica
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spelling Pan-cancer analysis of whole genomesICGC/TCGA Pan-Cancer Analysis of Whole Genomes ConsortiumDemidov, German, 1990-Drechsel, OliverOssowski, StephanEstivill, Xavier, 1955-Escaramís, GeòrgiaBosio, MattiaHolik, Aliaksei Z.Sušak, Hana, 1985-Rabionet Janssen, RaquelStobbe, Miranda D.Marquès i Bonet, Tomàs, 1975-Navarro i Cuartiellas, Arcadi, 1969-Gut, Ivo GlynneBeltran, SergiGut, MartaTrotta, Jean-RemiWhalley, Justin P.Heath, SimonPrasad, AparnaHeredia Genestar, José María, 1985-Sabarinathan, RadhakrishnanPich Roselló, Oriol, 1992-Gonzalez-Perez, AbelRubio Pérez, Carlota, 1990-Tamborero Noguera, DavidMularoni, LorisDeu-Pons, JordiMuiños, FerranMuyas Remolar, Francesc, 1992-CàncerGenòmicaGenèticaCancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes.Nature Research202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44263http://dx.doi.org/10.1038/s41586-020-1969-6reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature. 2020 Feb;578(7793):82-93© 2020 German M. Deminov et al. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were madehttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/442632026-05-29T05:05:01Z
dc.title.none.fl_str_mv Pan-cancer analysis of whole genomes
title Pan-cancer analysis of whole genomes
spellingShingle Pan-cancer analysis of whole genomes
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Càncer
Genòmica
Genètica
title_short Pan-cancer analysis of whole genomes
title_full Pan-cancer analysis of whole genomes
title_fullStr Pan-cancer analysis of whole genomes
title_full_unstemmed Pan-cancer analysis of whole genomes
title_sort Pan-cancer analysis of whole genomes
dc.creator.none.fl_str_mv ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Demidov, German, 1990-
Drechsel, Oliver
Ossowski, Stephan
Estivill, Xavier, 1955-
Escaramís, Geòrgia
Bosio, Mattia
Holik, Aliaksei Z.
Sušak, Hana, 1985-
Rabionet Janssen, Raquel
Stobbe, Miranda D.
Marquès i Bonet, Tomàs, 1975-
Navarro i Cuartiellas, Arcadi, 1969-
Gut, Ivo Glynne
Beltran, Sergi
Gut, Marta
Trotta, Jean-Remi
Whalley, Justin P.
Heath, Simon
Prasad, Aparna
Heredia Genestar, José María, 1985-
Sabarinathan, Radhakrishnan
Pich Roselló, Oriol, 1992-
Gonzalez-Perez, Abel
Rubio Pérez, Carlota, 1990-
Tamborero Noguera, David
Mularoni, Loris
Deu-Pons, Jordi
Muiños, Ferran
Muyas Remolar, Francesc, 1992-
author ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
author_facet ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Demidov, German, 1990-
Drechsel, Oliver
Ossowski, Stephan
Estivill, Xavier, 1955-
Escaramís, Geòrgia
Bosio, Mattia
Holik, Aliaksei Z.
Sušak, Hana, 1985-
Rabionet Janssen, Raquel
Stobbe, Miranda D.
Marquès i Bonet, Tomàs, 1975-
Navarro i Cuartiellas, Arcadi, 1969-
Gut, Ivo Glynne
Beltran, Sergi
Gut, Marta
Trotta, Jean-Remi
Whalley, Justin P.
Heath, Simon
Prasad, Aparna
Heredia Genestar, José María, 1985-
Sabarinathan, Radhakrishnan
Pich Roselló, Oriol, 1992-
Gonzalez-Perez, Abel
Rubio Pérez, Carlota, 1990-
Tamborero Noguera, David
Mularoni, Loris
Deu-Pons, Jordi
Muiños, Ferran
Muyas Remolar, Francesc, 1992-
author_role author
author2 Demidov, German, 1990-
Drechsel, Oliver
Ossowski, Stephan
Estivill, Xavier, 1955-
Escaramís, Geòrgia
Bosio, Mattia
Holik, Aliaksei Z.
Sušak, Hana, 1985-
Rabionet Janssen, Raquel
Stobbe, Miranda D.
Marquès i Bonet, Tomàs, 1975-
Navarro i Cuartiellas, Arcadi, 1969-
Gut, Ivo Glynne
Beltran, Sergi
Gut, Marta
Trotta, Jean-Remi
Whalley, Justin P.
Heath, Simon
Prasad, Aparna
Heredia Genestar, José María, 1985-
Sabarinathan, Radhakrishnan
Pich Roselló, Oriol, 1992-
Gonzalez-Perez, Abel
Rubio Pérez, Carlota, 1990-
Tamborero Noguera, David
Mularoni, Loris
Deu-Pons, Jordi
Muiños, Ferran
Muyas Remolar, Francesc, 1992-
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer
Genòmica
Genètica
topic Càncer
Genòmica
Genètica
description Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44263
http://dx.doi.org/10.1038/s41586-020-1969-6
url http://hdl.handle.net/10230/44263
http://dx.doi.org/10.1038/s41586-020-1969-6
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature. 2020 Feb;578(7793):82-93
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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