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Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
journal contribution
posted on 2023-08-30, 10:02 authored by Isidro Cortés-Ciriano, Jake June-Koo Lee, Ruibin Xi, Dhawal Jain, Youngsook L Jung, Lixing Yang, Dmitry Gordenin, Leszek J Klimczak, Cheng-Zhong Zhang, David S Pellman, Kadir C Akdemir, Eva G Alvarez, Adrian Baez-Ortega, Rameen Beroukhim, Paul C Boutros, David DL Bowtell, Benedikt Brors, Kathleen H Burns, Peter J Campbell, Kin Chan, Ken Chen, Ana Dueso-Barroso, Andrew J Dunford, Paul A Edwards, Xavier Estivill, Dariush Etemadmoghadam, Lars Feuerbach, J Lynn Fink, Milana Frenkel-Morgenstern, Dale W Garsed, Mark Gerstein, Dmitry A Gordenin, David Haan, James E Haber, Julian M Hess, Barbara Hutter, Marcin Imielinski, David TW Jones, Young Seok Ju, Marat D Kazanov, Youngil Koh, Jan O Korbel, Kiran Kumar, Eunjung Alice Lee, Yilong Li, Andy G Lynch, Geoff Macintyre, Florian Markowetz, Iñigo Martincorena, Alexander Martinez-Fundichely, Satoru Miyano, Hidewaki Nakagawa, Fabio CP Navarro, Stephan Ossowski, Peter J Park, John V Pearson, Montserrat Puiggròs, Karsten Rippe, Nicola D Roberts, Steven A Roberts, Bernardo Rodriguez-Martin, Steven E Schumacher, Ralph Scully, Mark Shackleton, Nikos Sidiropoulos, Lina Sieverling, Chip Stewart, David Torrents, Jose MC Tubio, Izar Villasante, Nicola Waddell, Jeremiah A Wala, Joachim Weischenfeldt, Xiaotong Yao, Sung-Soo Yoon, Jorge Zamora, Lauri A Aaltonen, Federico Abascal, Adam Abeshouse, Hiroyuki Aburatani, David J Adams, Nishant Agrawal, Keun Soo Ahn, Sung-Min Ahn, Hiroshi Aikata, Rehan Akbani, Hikmat Al-Ahmadie, Sultan T Al-Sedairy, Fatima Al-Shahrour, Malik Alawi, Monique Albert, Kenneth Aldape, Ludmil B Alexandrov, Adrian Ally, Kathryn Alsop, Fernanda Amary, Samirkumar B Amin, Brice Aminou, Ole Ammerpohl, Matthew J Anderson, Yeng Ang, Davide Antonello, Pavana Anur, Samuel Aparicio, Elizabeth L Appelbaum, Yasuhito Arai, Axel Aretz, Koji Arihiro, Shun-ichi Ariizumi, Joshua Armenia, Laurent Arnould, Sylvia Asa, Yassen Assenov, Gurnit Atwal, Sietse Aukema, J Todd Auman, Miriam RR Aure, Philip Awadalla, Marta Aymerich, Gary D Bader, Matthew H Bailey, Peter J Bailey, Miruna Balasundaram, Saianand Balu, Pratiti Bandopadhayay, Rosamonde E Banks, Stefano Barbi, Andrew P Barbour, Jonathan Barenboim, Jill Barnholtz-Sloan, Hugh Barr, Elisabet Barrera, John Bartlett, Javier Bartolome, Claudio Bassi, Oliver F Bathe, Daniel Baumhoer, Prashant Bavi, Stephen B Baylin, Wojciech Bazant, Duncan Beardsmore, Timothy A Beck, Sam Behjati, Andreas Behren, Beifang Niu, Cindy Bell, Sergi Beltran, Christopher Benz, Andrew Berchuck, Anke K Bergmann, Erik N Bergstrom, Benjamin P Berman, Daniel M Berney, Stephan H Bernhart, Mario Berrios, Samantha Bersani, Johanna Bertl, Miguel Betancourt, Vinayak Bhandari, Shriram G Bhosle, Andrew V Biankin, Matthias Bieg, Darell Bigner, Hans Binder, Ewan Birney, Michael Birrer, Nidhan K Biswas, Bodil Bjerkehagen, Tom Bodenheimer, Lori Boice, Giada Bonizzato, Johann S De Bono, Arnoud Boot, Moiz S Bootwalla, Ake Borg, Arndt Borkhardt, Keith A Boroevich, Ivan Borozan, Christoph Borst, Marcus Bosenberg, Mattia Bosio, Jacqueline Boultwood, Guillaume Bourque, G Steven Bova, David T Bowen, Reanne Bowlby, Sandrine Boyault, Rich Boyce, Jeffrey Boyd, Alvis Brazma, Paul Brennan, Daniel S Brewer, Arie B Brinkman, Robert G Bristow, Russell R Broaddus, Jane E Brock, Malcolm Brock, Annegien Broeks, Angela N Brooks, Denise Brooks, Søren Brunak, Timothy JC Bruxner, Alicia L Bruzos, Alex Buchanan, Ivo Buchhalter, Christiane Buchholz, Susan Bullman, Hazel Burke, Birgit Burkhardt, John Busanovich, Carlos D Bustamante, Adam P Butler, Atul J Butte, Niall J Byrne, Anne-Lise Børresen-Dale, Samantha J Caesar-Johnson, Andy Cafferkey, Declan Cahill, Claudia Calabrese, Carlos Caldas, Fabien Calvo, Niedzica Camacho, Elias Campo, Cinzia Cantù, Shaolong Cao, Thomas E Carey, Joana Carlevaro-Fita, Rebecca Carlsen, Ivana Cataldo, Mario Cazzola, Jonathan Cebon, Robert Cerfolio, Dianne E Chadwick, Dimple Chakravarty, Don Chalmers, Calvin Wing Yiu Chan, Michelle Chan-Seng-Yue, Vishal S Chandan, David K Chang, Stephen J Chanock, Lorraine A Chantrill, Aurélien Chateigner, Nilanjan Chatterjee, Kazuaki Chayama, Hsiao-Wei Chen, Jieming Chen, Yiwen Chen, Zhaohong Chen, Andrew D Cherniack, Jeremy Chien, Yoke-Eng Chiew, Suet-Feung Chin, Juok Cho, Sunghoon Cho, Jung Kyoon Choi, Wan Choi, Christine Chomienne, Zechen Chong, Su Pin Choo, Angela Chou, Angelika N Christ, Elizabeth L Christie, Eric Chuah, Carrie Cibulskis, Kristian Cibulskis, Sara Cingarlini, Peter Clapham, Alexander Claviez, Sean Cleary, Nicole Cloonan, Marek Cmero, Colin C Collins, Ashton A Connor, Susanna L Cooke, Colin S Cooper, Leslie Cope, Vincenzo Corbo, Matthew G Cordes, Stephen M Cordner, Kyle Covington, Prue A Cowin, Brian Craft, David Craft, Chad J Creighton, Yupeng Cun, Erin Curley, Ioana Cutcutache, Karolina Czajka, Bogdan Czerniak, Rebecca A Dagg, Ludmila Danilova, Maria Vittoria Davi, Natalie R Davidson, Helen Davies, Ian J Davis, Brandi N Davis-Dusenbery, Kevin J Dawson, Francisco M De La Vega, Ricardo De Paoli-Iseppi, Timothy Defreitas, Angelo P Dei Tos, Olivier Delaneau, John A Demchok, Jonas Demeulemeester, German M Demidov, Deniz Demircioğlu, Nening M Dennis, Robert E Denroche, Stefan C Dentro, Nikita Desai, Vikram Deshpande, Amit G Deshwar, Christine Desmedt, Jordi Deu-Pons, Noreen Dhalla, Neesha C Dhani, Priyanka Dhingra, Rajiv Dhir, Anthony DiBiase, Klev Diamanti, Li Ding, Shuai Ding, Huy Q Dinh, Luc Dirix, HarshaVardhan Doddapaneni, Nilgun Donmez, Michelle T Dow, Ronny Drapkin, Oliver Drechsel, Ruben M Drews, Serge Serge, Tim Dudderidge, Michael Dunn, Lewis Jonathan Dursi, Fraser R Duthie, Ken Dutton-Regester, Jenna Eagles, Douglas F Easton, Stuart Edmonds, Sandra E Edwards, Rosalind A Eeles, Anna Ehinger, Juergen Eils, Roland Eils, Adel El-Naggar, Matthew Eldridge, Kyle Ellrott, Serap Erkek, Georgia Escaramis, Shadrielle MG Espiritu, Jorunn E Eyfjord, Bishoy M Faltas, Daiming Fan, Yu Fan, William C Faquin, Claudiu Farcas, Matteo Fassan, Aquila Fatima, Francesco Favero, Nodirjon Fayzullaev, Ina Felau, Sian Fereday, Martin L Ferguson, Vincent Ferretti, Matthew A Field, Gaetano Finocchiaro, Cyril Fisher, Matthew W Fittall, Anna Fitzgerald, Rebecca C Fitzgerald, Adrienne M Flanagan, Neil E Fleshner, Paul Flicek, John A Foekens, Kwun M Fong, Nuno A Fonseca, Christopher S Foster, Natalie S Fox, Michael Fraser, Scott Frazer, William Friedman, Joan Frigola, Catrina C Fronick, Akihiro Fujimoto, Masashi Fujita, Masashi Fukayama, Lucinda A Fulton, Robert S Fulton, Mayuko Furuta, P Andrew Futreal, Anja Füllgrabe, Stacey B Gabriel, Steven Gallinger, Carlo Gambacorti-Passerini, Jianjiong Gao, Shengjie Gao, Levi Garraway, Øystein Garred, Erik Garrison, Nils Gehlenborg, Josep LL Gelpi, Joshy George, Daniela S Gerhard, Clarissa Gerhauser, Jeffrey E Gershenwald, Moritz Gerstung, Gad Getz, Mohammed Ghori, Ronald Ghossein, Nasra H Giama, Richard A Gibbs, Bob Gibson, Anthony J Gill, Pelvender Gill, Dilip D Giri, Dominik Glodzik, Vincent J Gnanapragasam, Maria Elisabeth Goebler, Mary J Goldman, Carmen Gomez, Santiago Gonzalez, Abel Gonzalez-Perez, James Gossage, Kunihito Gotoh, Ramaswamy Govindan, Dorthe Grabau, Janet S Graham, Robert C Grant, Anthony R Green, Eric Green, Liliana Greger, Nicola Grehan, Sonia Grimaldi, Sean M Grimmond, Robert L Grossman, Adam Grundhoff, Gunes Gundem, Qianyun Guo, Manaswi Gupta, Shailja Gupta, Ivo G Gut, Marta Gut, Jonathan Göke, Gavin Ha, Andrea Haake, Siegfried Haas, Kerstin Haase, Nina Habermann, Faraz Hach, Syed Haider, Natsuko Hama, Freddie C Hamdy, Anne Hamilton, Mark P Hamilton, Leng Han, George B Hanna, Martin Hansmann, Nicholas J Haradhvala, Olivier Harismendy, Ivon Harliwong, Arif O Harmanci, Eoghan Harrington, Takanori Hasegawa, David Haussler, Steve Hawkins, Shinya Hayami, Shuto Hayashi, D Neil Hayes, Stephen J Hayes, Nicholas K Hayward, Steven Hazell, Yao He, Allison P Heath, Simon C Heath, David Hedley, Apurva M Hegde, David I Heiman, Michael C Heinold, Zachary Heins, Lawrence E Heisler, Eva Hellstrom-Lindberg, Mohamed Helmy, Seong Gu Heo, Austin J Hepperla, José María Heredia-Genestar, Carl Herrmann, Peter Hersey, Holmfridur Hilmarsdottir, Jonathan Hinton, Satoshi Hirano, Nobuyoshi Hiraoka, Katherine A Hoadley, Asger Hobolth, Ermin Hodzic, Jessica I Hoell, Steve Hoffmann, Oliver Hofmann, Andrea Holbrook, Aliaksei Z Holik, Michael A HollingsworthChromothripsis 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.
