Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these f...

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Autores: Akdemir, Kadir C., Le, Victoria T., Chandran, Sahaana, Li, Yilong, Verhaak, Roel G., Beroukhim, Rameen, Campbell, Peter J., Chin, Linda, PCAWG Structural Variation Working Group, Dixon, Jesse R., Futreal, P. Andrew, PCAWG Consortium, Ossowski, Stephan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/44339
Acceso en línea:http://hdl.handle.net/10230/44339
http://dx.doi.org/10.1038/s41588-019-0564-y
Access Level:acceso abierto
Palabra clave:Genètica
Cromatina
Reordenament genètic
Genoma humà
Tumors
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spelling Disruption of chromatin folding domains by somatic genomic rearrangements in human cancerAkdemir, Kadir C.Le, Victoria T.Chandran, SahaanaLi, YilongVerhaak, Roel G.Beroukhim, RameenCampbell, Peter J.Chin, LindaPCAWG Structural Variation Working GroupDixon, Jesse R.Futreal, P. AndrewPCAWG ConsortiumOssowski, StephanGenèticaCromatinaReordenament genèticGenoma humàTumorsChromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.This work was supported by a Cancer Prevention Research Institute of Texas award (R1205), the Welch Foundation’s Robert A. Welch Distinguished Chair Award (G-0040 to P.A.F.) and the Emerson Collective Cancer Research Fund (to K.C.A.). J.R.D. is supported by an NIH Director’s Early Independence Award (DP5OD023071)Nature Research202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44339http://dx.doi.org/10.1038/s41588-019-0564-yreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNature Genetics. 2020 Mar;52(3):294-305© Kadir C. Akdemir et al. Open Access 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:repositori.upf.edu:10230/443392026-06-12T07:21:37Z
dc.title.none.fl_str_mv Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
title Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
spellingShingle Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
Akdemir, Kadir C.
Genètica
Cromatina
Reordenament genètic
Genoma humà
Tumors
title_short Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
title_full Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
title_fullStr Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
title_full_unstemmed Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
title_sort Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
dc.creator.none.fl_str_mv Akdemir, Kadir C.
Le, Victoria T.
Chandran, Sahaana
Li, Yilong
Verhaak, Roel G.
Beroukhim, Rameen
Campbell, Peter J.
Chin, Linda
PCAWG Structural Variation Working Group
Dixon, Jesse R.
Futreal, P. Andrew
PCAWG Consortium
Ossowski, Stephan
author Akdemir, Kadir C.
author_facet Akdemir, Kadir C.
Le, Victoria T.
Chandran, Sahaana
Li, Yilong
Verhaak, Roel G.
Beroukhim, Rameen
Campbell, Peter J.
Chin, Linda
PCAWG Structural Variation Working Group
Dixon, Jesse R.
Futreal, P. Andrew
PCAWG Consortium
Ossowski, Stephan
author_role author
author2 Le, Victoria T.
Chandran, Sahaana
Li, Yilong
Verhaak, Roel G.
Beroukhim, Rameen
Campbell, Peter J.
Chin, Linda
PCAWG Structural Variation Working Group
Dixon, Jesse R.
Futreal, P. Andrew
PCAWG Consortium
Ossowski, Stephan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Genètica
Cromatina
Reordenament genètic
Genoma humà
Tumors
topic Genètica
Cromatina
Reordenament genètic
Genoma humà
Tumors
description Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.
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/10230/44339
http://dx.doi.org/10.1038/s41588-019-0564-y
url http://hdl.handle.net/10230/44339
http://dx.doi.org/10.1038/s41588-019-0564-y
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature Genetics. 2020 Mar;52(3):294-305
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:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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