@article{948982f25f3c4903921d6878d177dd3c,
title = "Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer",
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.",
author = "{PCAWG-Structural Variation Working Group} and {PCAWG Consortium} and Akdemir, {Kadir C.} and Le, {Victoria T.} and Sahaana Chandran and Yilong Li and Verhaak, {Roel G.} and Rameen Beroukhim and Campbell, {Peter J.} and Lynda Chin and Dixon, {Jesse R.} and Futreal, {P. Andrew} and Akdemir, {Kadir C.} and Alvarez, {Eva G.} and Adrian Baez-Ortega and Boutros, {Paul C.} and Bowtell, {David D.L.} and Benedikt Brors and Burns, {Kathleen H.} and Campbell, {Peter J.} and Kin Chan and Ken Chen and Isidro Cort{\'e}s-Ciriano and Ana Dueso-Barroso and Dunford, {Andrew J.} and Edwards, {Paul A.} and Xavier Estivill and Dariush Etemadmoghadam and Lars Feuerbach and Fink, {J. Lynn} and Milana Frenkel-Morgenstern and Garsed, {Dale W.} and Mark Gerstein and Gordenin, {Dmitry A.} and David Haan and Haber, {James E.} and Hess, {Julian M.} and Barbara Hutter and Marcin Imielinski and Jones, {David T.W.} and Ju, {Young Seok} and Kazanov, {Marat D.} and Klimczak, {Leszek J.} and Youngil Koh and Korbel, {Jan O.} and Kiran Kumar and Lee, {Eunjung Alice} and Lee, {Jake June Koo} and Yilong Li and Lynch, {Andy G.} and Geoff Macintyre and Connor, {Ashton A.}",
note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = mar,
day = "1",
doi = "10.1038/s41588-019-0564-y",
language = "English (US)",
volume = "52",
pages = "294--305",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",
}