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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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