Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer.
Authors
Akdemir, Kadir C
Le, Victoria T
Chandran, Sahaana
Li, Yilong
Verhaak, Roel G
Beroukhim, Rameen
Campbell, Peter J
Chin, Lynda
Dixon, Jesse R
PCAWG Structural Variation Working Group
PCAWG Consortium
Publication Date
2020-03Journal Title
Nat Genet
ISSN
1061-4036
Publisher
Springer Science and Business Media LLC
Volume
52
Issue
3
Pages
294-305
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Akdemir, K. C., Le, V. T., Chandran, S., Li, Y., Verhaak, R. G., Beroukhim, R., Campbell, P. J., et al. (2020). Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer.. Nat Genet, 52 (3), 294-305. https://doi.org/10.1038/s41588-019-0564-y
Abstract
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.
Keywords
Article, /631/114/2164, /631/67, /631/208/199, /45, /45/15, /38/91, /9, article
Sponsorship
Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) (R1205)
Welch Foundation (G-0040)
Identifiers
s41588-019-0564-y, 564
External DOI: https://doi.org/10.1038/s41588-019-0564-y
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317147
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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