Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer...

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Autores: Rheinbay, Esther, Sabarinathan, Radhakrishnan, Mularoni, Loris, Gonzalez-Perez, Abel, Pich Roselló, Oriol, 1992-, Tamborero Noguera, David, López Bigas, Núria, Getz, Gad, PCAWG Consortium
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:10230/44262
Acceso en línea:http://hdl.handle.net/10230/44262
http://dx.doi.org/10.1038/s41586-020-1965-x
Access Level:acceso abierto
Palabra clave:Genoma humà
Tumors -- Genètica
Mutació (Biologia)
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spelling Analyses of non-coding somatic drivers in 2,658 cancer whole genomesRheinbay, EstherSabarinathan, RadhakrishnanMularoni, LorisGonzalez-Perez, AbelPich Roselló, Oriol, 1992-Tamborero Noguera, DavidLópez Bigas, NúriaGetz, GadPCAWG ConsortiumGenoma humàTumors -- GenèticaMutació (Biologia)The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.Work in the Getz laboratory was partially funded by the GDAC grants (NIH U24CA143845 and NIH U24CA210999), G.G.’s funds at the Broad Institute and MGH. J.S.P. was partially funded by Independent Research Fund Denmark (12-126439 and 7016-00379) and The Danish Cancer Society (R124-A7869). R.B. received funds from the National Institutes of Health (U54CA143798, R01CA188228, R35GM127029, and R01CA215489). J.W. was partly funded by Independent Research Fund Denmark (4183-00233B and 8020-00282B) and Danish Cancer Society (R147-Rp12977). N.L.-B. acknowledges funding from the European Research Council consolidator grant 682398) and Spanish Ministry of Economy and Competitiveness (SAF2015-66084-R, MINECO/FEDER, UE)Nature Research202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44262http://dx.doi.org/10.1038/s41586-020-1965-xreponame: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): 102-11info:eu-repo/grantAgreement/EC/H2020/682398info:eu-repo/grantAgreement/ES/1PE/SAF2015-66084-R© 2020 Esther Rheinbay 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:10230/442622026-05-29T05:05:01Z
dc.title.none.fl_str_mv Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
title Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
spellingShingle Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
Rheinbay, Esther
Genoma humà
Tumors -- Genètica
Mutació (Biologia)
title_short Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
title_full Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
title_fullStr Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
title_full_unstemmed Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
title_sort Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
dc.creator.none.fl_str_mv Rheinbay, Esther
Sabarinathan, Radhakrishnan
Mularoni, Loris
Gonzalez-Perez, Abel
Pich Roselló, Oriol, 1992-
Tamborero Noguera, David
López Bigas, Núria
Getz, Gad
PCAWG Consortium
author Rheinbay, Esther
author_facet Rheinbay, Esther
Sabarinathan, Radhakrishnan
Mularoni, Loris
Gonzalez-Perez, Abel
Pich Roselló, Oriol, 1992-
Tamborero Noguera, David
López Bigas, Núria
Getz, Gad
PCAWG Consortium
author_role author
author2 Sabarinathan, Radhakrishnan
Mularoni, Loris
Gonzalez-Perez, Abel
Pich Roselló, Oriol, 1992-
Tamborero Noguera, David
López Bigas, Núria
Getz, Gad
PCAWG Consortium
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Genoma humà
Tumors -- Genètica
Mutació (Biologia)
topic Genoma humà
Tumors -- Genètica
Mutació (Biologia)
description The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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/10230/44262
http://dx.doi.org/10.1038/s41586-020-1965-x
url http://hdl.handle.net/10230/44262
http://dx.doi.org/10.1038/s41586-020-1965-x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature. 2020 Feb; 578(7793): 102-11
info:eu-repo/grantAgreement/EC/H2020/682398
info:eu-repo/grantAgreement/ES/1PE/SAF2015-66084-R
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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