Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
Creators: name: Akdemir, Kadir C
name: Le, Victoria T
name: Chandran, Sahaana
name: Li, Yilong
name: Verhaak, Roel G
name: Beroukhim, Rameen
name: Campbell, Peter J
name: Chin, Lynda
name: Dixon, Jesse R
name: Futreal, P Andrew
name: Alvarez, Eva G
name: Baez-Ortega, Adrian
name: Boutros, Paul C
name: Bowtell, David DL
name: Brors, Benedikt
name: Burns, Kathleen H
name: Chan, Kin
name: Chen, Ken
name: Cortés-Ciriano, Isidro
name: Dueso-Barroso, Ana
name: Dunford, Andrew J
name: Edwards, Paul A
name: Estivill, Xavier
name: Etemadmoghadam, Dariush
name: Feuerbach, Lars
name: Fink, J Lynn
name: Frenkel-Morgenstern, Milana
name: Garsed, Dale W
name: Gerstein, Mark
name: Gordenin, Dmitry A
name: Haan, David
name: Haber, James E
name: Hess, Julian M
name: Hutter, Barbara
name: Imielinski, Marcin
name: Jones, David TW
name: Ju, Young Seok
name: Kazanov, Marat D
name: Klimczak, Leszek J
name: Koh, Youngil
name: Korbel, Jan O
name: Kumar, Kiran
name: Lee, Eunjung Alice
name: Lee, Jake June-Koo
name: Lynch, Andy G
name: Macintyre, Geoff
name: Markowetz, Florian
name: Martincorena, Iñigo
name: Martinez-Fundichely, Alexander
name: Meyerson, Matthew
name: Miyano, Satoru
name: Nakagawa, Hidewaki
name: Navarro, Fabio CP
name: Ossowski, Stephan
name: Park, Peter J
name: Pearson, John V
name: Puiggròs, Montserrat
name: Rippe, Karsten
name: Roberts, Nicola D
name: Roberts, Steven A
name: Rodriguez-Martin, Bernardo
name: Schumacher, Steven E
name: Scully, Ralph
name: Shackleton, Mark
name: Sidiropoulos, Nikos
name: Sieverling, Lina
name: Stewart, Chip
name: Torrents, David
name: MC Tubio, Jose
name: Villasante, Izar
name: Waddell, Nicola
name: Wala, Jeremiah A
name: Weischenfeldt, Joachim
name: Yang, Lixing
name: Yao, Xiaotong
name: Yoon, Sung-Soo
name: Zamora, Jorge
name: Zhang, Cheng-Zhong
name: Aaltonen, Lauri A
name: Abascal, Federico
name: Abeshouse, Adam
name: Aburatani, Hiroyuki
name: Adams, David J
name: Agrawal, Nishant
name: Ahn, Keun Soo
name: Ahn, Sung-Min
name: Aikata, Hiroshi
name: Akbani, Rehan
name: Al-Ahmadie, Hikmat
name: Al-Sedairy, Sultan T
name: Al-Shahrour, Fatima
name: Alawi, Malik
name: Albert, Monique
name: Aldape, Kenneth
name: Alexandrov, Ludmil B
name: Ally, Adrian
name: Alsop, Kathryn
name: Amary, Fernanda
name: Amin, Samirkumar B
name: Aminou, Brice
name: Ammerpohl, Ole
name: Anderson, Matthew J
name: Ang, Yeng
name: Antonello, Davide
name: Anur, Pavana
name: Aparicio, Samuel
name: Appelbaum, Elizabeth L
name: Arai, Yasuhito
name: Aretz, Axel
name: Arihiro, Koji
name: Ariizumi, Shun-ichi
name: Armenia, Joshua
name: Arnould, Laurent
name: Asa, Sylvia
name: Assenov, Yassen
name: Atwal, Gurnit
name: Aukema, Sietse
name: Auman, J Todd
name: Aure, Miriam RR
name: Awadalla, Philip
name: Aymerich, Marta
name: Bader, Gary D
name: Bailey, Matthew H
name: Bailey, Peter J
name: Balasundaram, Miruna
name: Balu, Saianand
name: Bandopadhayay, Pratiti
name: Banks, Rosamonde E
name: Barbi, Stefano
name: Barbour, Andrew P
name: Barenboim, Jonathan
name: Barnholtz-Sloan, Jill
name: Barr, Hugh
name: Barrera, Elisabet
name: Bartlett, John
name: Bartolome, Javier
name: Bassi, Claudio
name: Bathe, Oliver F
name: Baumhoer, Daniel
name: Bavi, Prashant
name: Baylin, Stephen B
name: Bazant, Wojciech
name: Beardsmore, Duncan
name: Beck, Timothy A
name: Behjati, Sam
name: Behren, Andreas
name: Niu, Beifang
name: Bell, Cindy
name: Beltran, Sergi
name: Benz, Christopher
name: Berchuck, Andrew
name: Bergmann, Anke K
name: Bergstrom, Erik N
name: Berman, Benjamin P
name: Berney, Daniel M
name: Bernhart, Stephan H
name: Berrios, Mario
name: Bersani, Samantha
name: Bertl, Johanna
name: Betancourt, Miguel
name: Bhandari, Vinayak
name: Bhosle, Shriram G
name: Biankin, Andrew V
name: Bieg, Matthias
name: Bigner, Darell
name: Binder, Hans
name: Birney, Ewan
name: Birrer, Michael
name: Biswas, Nidhan K
name: Bjerkehagen, Bodil
name: Bodenheimer, Tom
name: Boice, Lori
name: Bonizzato, Giada
name: De Bono, Johann S
name: Boot, Arnoud
name: Bootwalla, Moiz S
name: Borg, Ake
name: Borkhardt, Arndt
name: Boroevich, Keith A
name: Borozan, Ivan
name: Borst, Christoph
name: Bosenberg, Marcus
name: Bosio, Mattia
name: Boultwood, Jacqueline
name: Bourque, Guillaume
name: Bova, G Steven
name: Bowen, David T
name: Bowlby, Reanne
name: Boyault, Sandrine
name: Boyce, Rich
name: Boyd, Jeffrey
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name: Brennan, Paul
name: Brewer, Daniel S
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name: Bristow, Robert G
name: Broaddus, Russell R
name: Brock, Jane E
name: Brock, Malcolm
name: Broeks, Annegien
name: Brooks, Angela N
name: Brooks, Denise
name: Brunak, Søren
name: Bruxner, Timothy JC
name: Bruzos, Alicia L
name: Buchanan, Alex
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name: Buchholz, Christiane
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name: Carlevaro-Fita, Joana
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name: Cazzola, Mario
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name: Chakravarty, Dimple
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name: Chang, David K
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name: Chantrill, Lorraine A
name: Chateigner, Aurélien
name: Chatterjee, Nilanjan
name: Chayama, Kazuaki
name: Chen, Hsiao-Wei
name: Chen, Jieming
name: Chen, Yiwen
name: Chen, Zhaohong
name: Cherniack, Andrew D
name: Chien, Jeremy
name: Chiew, Yoke-Eng
name: Chin, Suet-Feung
name: Cho, Juok
name: Cho, Sunghoon
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name: Choi, Wan
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name: Chong, Zechen
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name: Chou, Angela
name: Christ, Angelika N
name: Christie, Elizabeth L
name: Chuah, Eric
name: Cibulskis, Carrie
name: Cibulskis, Kristian
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name: Cope, Leslie
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name: Cordner, Stephen M
name: Covington, Kyle
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name: Craft, Brian
name: Craft, David
name: Creighton, Chad J
name: Cun, Yupeng
name: Curley, Erin
name: Cutcutache, Ioana
name: Czajka, Karolina
name: Czerniak, Bogdan
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name: Danilova, Ludmila
name: Davi, Maria Vittoria
name: Davidson, Natalie R
name: Davies, Helen
name: Davis, Ian J
name: Davis-Dusenbery, Brandi N
name: Dawson, Kevin J
name: De La Vega, Francisco M
name: De Paoli-Iseppi, Ricardo
name: Defreitas, Timothy
name: Dei Tos, Angelo P
name: Delaneau, Olivier
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name: Demeulemeester, Jonas
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name: Demircioğlu, Deniz
name: Dennis, Nening M
name: Denroche, Robert E
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name: Dhalla, Noreen
name: Dhani, Neesha C
name: Dhingra, Priyanka
name: Dhir, Rajiv
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name: Ding, Li
name: Ding, Shuai
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name: Gao, Shengjie
name: Garraway, Levi
name: Garred, Øystein
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name: George, Joshy
name: Gerhard, Daniela S
name: Gerhauser, Clarissa
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name: Glodzik, Dominik
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name: Graham, Janet S
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name: Hoadley, Katherine A
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name: Imbusch, Charles David
name: Imoto, Seiya
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name: Isaev, Keren
name: Ishikawa, Shumpei
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name: Islam, SM Ashiqul
name: Ittmann, Michael
name: Ivkovic, Sinisa
name: Izarzugaza, Jose MG
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name: Jakrot, Valerie
name: Jamieson, Nigel B
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name: Kabbe, Rolf
name: Kahles, Andre
name: Kahraman, Abdullah
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name: Kakavand, Hojabr
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name: Kasaian, Katayoon
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name: Zhang, Junjun
name: Zhang, Xiuqing
name: Zhang, Xuanping
name: Zhang, Yan
name: Zhang, Zemin
name: Zhao, Zhongming
name: Zheng, Liangtao
name: Zheng, Xiuqing
name: Zhou, Wanding
name: Zhou, Yong
name: Zhu, Bin
name: Zhu, Hongtu
name: Zhu, Jingchun
name: Zhu, Shida
name: Zou, Lihua
name: Zou, Xueqing
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Publisher: name: The Francis Crick Institute
Year: 2023
Subjects: classificationCode: Tumour Biology
subject: Tumour Biology
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Genetics & Genomics
subject: Genetics &amp; Genomics
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology
classificationCode: Human Biology & Physiology
subject: Human Biology &amp; Physiology
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics

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.