TY - JOUR
T1 - Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
AU - PCAWG Structural Variation Working Group
AU - PCAWG Consortium
AU - Akdemir, Kadir C.
AU - Le, Victoria T.
AU - Chandran, Sahaana
AU - Li, Yilong
AU - Verhaak, Roel G.
AU - Beroukhim, Rameen
AU - Campbell, Peter J.
AU - Chin, Lynda
AU - Dixon, Jesse R.
AU - Futreal, P. Andrew
AU - Akdemir, Kadir C.
AU - Alvarez, Eva G.
AU - Baez-Ortega, Adrian
AU - Boutros, Paul C.
AU - Bowtell, David D.L.
AU - Brors, Benedikt
AU - Burns, Kathleen H.
AU - Campbell, Peter J.
AU - Chan, Kin
AU - Chen, Ken
AU - Cortés-Ciriano, Isidro
AU - Dueso-Barroso, Ana
AU - Dunford, Andrew J.
AU - Edwards, Paul A.
AU - Estivill, Xavier
AU - Etemadmoghadam, Dariush
AU - Feuerbach, Lars
AU - Fink, J. Lynn
AU - Frenkel-Morgenstern, Milana
AU - Garsed, Dale W.
AU - Gerstein, Mark
AU - Gordenin, Dmitry A.
AU - Haan, David
AU - Haber, James E.
AU - Hess, Julian M.
AU - Hutter, Barbara
AU - Imielinski, Marcin
AU - Jones, David T.W.
AU - Agrawal, Nishant
AU - Baylin, Stephen B.
AU - Brock, Malcolm
AU - Chatterjee, Nilanjan
AU - Cope, Leslie
AU - Danilova, Ludmila
AU - Hruban, Ralph H.
AU - Iacobuzio-Donahue, Christine A.
AU - Isaacs, William B.
AU - Richardson, Andrea L.
AU - Umbricht, Christopher
AU - Xu, Yanxun
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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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U2 - 10.1038/s41588-019-0564-y
DO - 10.1038/s41588-019-0564-y
M3 - Article
C2 - 32024999
AN - SCOPUS:85079073876
SN - 1061-4036
VL - 52
SP - 294
EP - 305
JO - Nature genetics
JF - Nature genetics
IS - 3
ER -