Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
Creators: name: Cortés-Ciriano, Isidro
name: Lee, Jake June-Koo
name: Xi, Ruibin
name: Jain, Dhawal
name: Jung, Youngsook L
name: Yang, Lixing
name: Gordenin, Dmitry
name: Klimczak, Leszek J
name: Zhang, Cheng-Zhong
name: Pellman, David S
name: Akdemir, Kadir C
name: Alvarez, Eva G
name: Baez-Ortega, Adrian
name: Beroukhim, Rameen
name: Boutros, Paul C
name: Bowtell, David DL
name: Brors, Benedikt
name: Burns, Kathleen H
name: Campbell, Peter J
name: Chan, Kin
name: Chen, Ken
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: Koh, Youngil
name: Korbel, Jan O
name: Kumar, Kiran
name: Lee, Eunjung Alice
name: Li, Yilong
name: Lynch, Andy G
name: Macintyre, Geoff
name: Markowetz, Florian
name: Martincorena, Iñigo
name: Martinez-Fundichely, Alexander
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: Yao, Xiaotong
name: Yoon, Sung-Soo
name: Zamora, Jorge
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
name: Brazma, Alvis
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name: Brewer, Daniel S
name: Brinkman, Arie B
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
name: Buchhalter, Ivo
name: Buchholz, Christiane
name: Bullman, Susan
name: Burke, Hazel
name: Burkhardt, Birgit
name: Busanovich, John
name: Bustamante, Carlos D
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name: Carlevaro-Fita, Joana
name: Carlsen, Rebecca
name: Cataldo, Ivana
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name: Cebon, Jonathan
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name: Chakravarty, Dimple
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name: Chan-Seng-Yue, Michelle
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name: Chang, David K
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name: Chantrill, Lorraine A
name: Chateigner, Aurélien
name: Chatterjee, Nilanjan
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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: Christie, Elizabeth L
name: Chuah, Eric
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name: Craft, David
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name: Cun, Yupeng
name: Curley, Erin
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name: Czajka, Karolina
name: Czerniak, Bogdan
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name: Danilova, Ludmila
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name: Davies, Helen
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name: Dawson, Kevin J
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name: De Paoli-Iseppi, Ricardo
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name: Demircioğlu, Deniz
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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: Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. 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), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.