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Yilong Li, Nicola D. Roberts, J. Wala, Ofer Shapira, S. Schumacher, K. Kumar, Ekta Khurana, Sebastian M. Waszak, J. Korbel, James E. Haber, Marcin Imieliński, Kadir C. Eva G. Adrian Rameen Paul C. David D. L. Benedi Akdemir Alvarez Baez-Ortega Beroukhim Boutros Bowt, K. Akdemir, Eva G. Álvarez, A. Baez-Ortega, R. Beroukhim, Paul C. Boutros, D. Bowtell, B. Brors, K. Burns, Peter J. Campbell, Kin Chan, Ken Chen, I. Cortés-Ciriano, Ana Dueso-Barroso, Andrew J. Dunford, Paul A. Edwards, X. Estivill, D. Etemadmoghadam, L. Feuerbach, J. L. Fink, M. Frenkel-Morgenstern, D. W. Garsed, Marc H. Gerstein, D. Gordenin, D. Haan, J. Hess, B. Hutter, Marcin Imieliński, David T. W. Jones, Young Seok Ju, M. Kazanov, L. Klimczak, Y. Koh, E. Lee, J. Lee, A. Lynch, G. Macintyre, Florian Markowetz, I. Martincorena, Alexander Martínez-Fundichely, Matthew Meyerson, Satoru Miyano, H. Nakagawa, Fábio C. P. Navarro, S. Ossowski, Peter J. Park, John V. Pearson, Montserrat Puiggrós, K. Rippe, S. Roberts, Bernardo Rodriguez-Martin, R. Scully, M. Shackleton, N. Sidiropoulos, L. Sieverling, C. Stewart, D. Torrents, J. Tubío, I. Villasante, Nicola Waddell, Joachim Weischenfeldt, Lixing Yang, Xiaotong Yao, S. Yoon, Jorge Zamora, Cheng-Zhong Zhang, Joachim Weischenfeldt, R. Beroukhim, Peter J. Campbell, Lauri A. Federico Adam Hiroyuki David J. Nishant Keun So Aaltonen Abascal Abeshouse Aburatani Adams Agrawal, L. Aaltonen, F. Abascal, Adam Abeshouse, H. Aburatani, D. Adams, N. Agrawal, K. Ahn, S. Ahn, H. Aikata, Rehan Akbani, H. Al-Ahmadie, S. Al-Sedairy, F. Al-Shahrour, M. Alawi, Monique Albert, K. Aldape, L. Alexandrov, Adrian Ally, K. Alsop, Eva G. Álvarez, F. Amary, S. Amin, Brice Aminou, O. Ammerpohl, M. Anderson, Y. Ang, D. Antonello, Pavana Anur, Samuel Aparicio, Elizabeth L. Appelbaum, Y. Arai, Axel Aretz, K. Arihiro, S. Ariizumi, J. Armenia, L. Arnould, S. Asa, Y. Assenov, Gurnit Atwal, S. Aukema, J. Auman, M. R. Aure, P. Awadalla, M. Aymerich, Gary D Bader, A. Baez-Ortega, Matthew H. Bailey, Peter Bailey, M. Balasundaram, S. Balu, P. Bandopadhayay, R. Banks, S. Barbi, A. Barbour, J. Barenboim, J. Barnholtz-Sloan, Hugh Barr, E. Barrera, John M. S. Bartlett, Javier Bartolome, C. Bassi, O. Bathe, D. Baumhoer, P. Bavi, S. Baylin, Wojciech Bazant, D. Beardsmore, Timothy A Beck, S. Behjati, A. Behren, Beifang Niu, C. Bell, S. Beltran, Christopher J. Benz, A. Berchuck, A. Bergmann, E. Bergstrom, B. Berman, D. Berney, S. Bernhart, R. Beroukhim, Mario Berrios, S. Bersani, Johanna Bertl, M. Betancourt, Vinayak Bhandari, S. Bhosle, A. Biankin, M. Bieg, D. Bigner, H. Binder, E. Birney, M. Birrer, N. Biswas, B. Bjerkehagen, T. Bodenheimer, L. Boice, G. Bonizzato, J. D. de Bono, Arnoud Boot, Moiz Bootwalla, Å. Borg, A. Borkhardt, Keith A. Boroevich, I. Borozan, Christoph Borst, M. Bosenberg, Mattia Bosio, J. Boultwood, G. Bourque, Paul C. Boutros, G. Bova, D. Bowen, R. Bowlby, D. Bowtell, S. Boyault, R. Boyce, Jeffrey H. Boyd, A. Brazma, P. Brennan, D. Brewer, A. Brinkman, Rob Bristow, R. Broaddus, J. Brock, M. Brock, A. Broeks, Angela N. Brooks, Denise Brooks, B. Brors, S. Brunak, T. Bruxner, A. Bruzos, Alex Buchanan, I. Buchhalter, C. Buchholz, S. Bullman, H. Burke, B. Burkhardt, K. Burns, John P. Busanovich, C. D. Bustamante, A. Butler, A. Butte, Niall J. Byrne, A. Børresen-Dale, Samantha J. Caesar-Johnson, Andy Cafferkey, D. Cahill, C. Calabrese, C. Caldas, F. Calvo, Niedzica Camacho, Peter J. Campbell, E. Campo, C. Cantù, S. Cao, T. Carey, Joana Carlevaro-Fita, R. Carlsen, I. Cataldo, M. Cazzola, J. Cebon, R. Cerfolio, D. Chadwick, D. Chakravarty, D. Chalmers, Calvin Wing Yiu Chan, Kin Chan, Michelle A. Chan-Seng-Yue, V. Chandan, D. Chang, S. Chanock, L. Chantrill, A. Chateigner, N. Chatterjee, K. Chayama, Hsiao-wei Chen, Jieming Chen, Yiwen Chen, Zhaohong Chen, A. Cherniack, J. Chien, Y. Chiew, S. Chin, Juok Cho, Sunghoon Cho, J. Choi, Wan Choi, C. Chomienne, Zechen Chong, S. Choo, A. Chou, Angelika N. Christ, E. Christie, E. Chuah, C. Cibulskis, K. Cibulskis, S. Cingarlini, P. Clapham, A. Claviez, S. Cleary, N. Cloonan, Marek Cmero, C. Collins, Ashton A Connor, S. Cooke, C. Cooper, L. Cope, V. Corbo, M. Cordes, S. Cordner, I. Cortés-Ciriano, K. Covington, P. Cowin, Brian Craft, David W Craft, C. Creighton, Yupeng Cun, Erin E. Curley, I. Cutcutache, Karolina M. Czajka, B. Czerniak, Rebecca A. Dagg, Ludmila V. Danilova, M. Davi’, Natalie R. Davidson, Helen R Davies, I. Davis, B. Davis-Dusenbery, K. Dawson, Francisco M. De La Vega, Ricardo De Paoli-Iseppi, T. DeFreitas, A. D. Tos, O. Delaneau, John A. Demchok, J. Demeulemeester, German M. Demidov, Deniz Demircioğlu, N. Dennis, R. Denroche, S. Dentro, N. Desai, V. Deshpande, A. Deshwar, C. Desmedt, J. Deu-Pons, Noreen Dhalla, N. Dhani, P. Dhingra, R. Dhir, Anthony Dibiase, K. Diamanti, L. Ding, Shuai Ding, Huy Q. Dinh, L. Dirix, H. Doddapaneni, Nilgun Donmez, Michelle Dow, R. Drapkin, O. Drechsel, Ruben M. Drews, Serge Serge, T. Dudderidge, Andrew J. Dunford, Michael Dunn, L. Dursi, F. Duthie, K. Dutton-Regester, Jenna Eagles, D. Easton, Stuart D. Edmonds, Paul A. Edwards, S. Edwards, R. Eeles, A. Ehinger, Juergen Eils, R. Eils, A. El-Naggar, M. Eldridge, K. Ellrott, S. Erkek, G. Escaramís, S. M. G. Espiritu, X. Estivill, D. Etemadmoghadam, J. Eyfjord, B. Faltas, D. Fan, Yu Fan, W. Faquin, Claudiu Farcas, M. Fassan, Aquila Fatima, F. Favero, Nodirjon Fayzullaev, Ina Felau, S. Fereday, M. Ferguson, Vincent Ferretti, M. Field, J. L. Fink, G. Finocchiaro, C. Fisher, M. Fittall, Anna M. Fitzgerald, R. Fitzgerald, A. Flanagan, N. Fleshner, Paul Flicek, J. Foekens, K. Fong, Nuno A. Fonseca, Christopher S. Foster, Natalie S. Fox, M. Fraser, S. Frazer, William Friedman, J. Frigola, C. Fronick, Akihiro Fujimoto, Masashi Fujita, M. Fukayama, L. Fulton, R. Fulton, Mayuko Furuta, P. Futreal, Anja Füllgrabe, S. Gabriel, S. Gallinger, C. Gambacorti-Passerini, Jianjiong Gao, Shengjie Gao, L. Garraway, Ø. Garred, Erik P. Garrison, D. W. Garsed, Nils Gehlenborg, J. Gelpí, J. George, D. Gerhard, C. Gerhauser, J. Gershenwald, Marc H. Gerstein, M. Gerstung, G. Getz, Mohammed J. R. Ghori, R. Ghossein, N. Giama, R. Gibbs, B. Gibson, A. Gill, P. Gill, D. Giri, D. Głodzik, V. Gnanapragasam, Maria Elisabeth Goebler, M. Goldman, Carmen Gomez, Santiago Gonzalez, A. González-Pérez, J. Gossage, K. Gotoh, R. Govindan, D. Grabau, J. S. Graham, R. Grant, A. Green, Eric D. Green, Liliana Greger, N. Grehan, Sonia Grimaldi, S. Grimmond, R. Grossman, A. Grundhoff, G. Gundem, Qianyun Guo, Manaswi Gupta, S. Gupta, I. Gut, M. Gut, Jonathan Göke, G. Ha, A. Haake, D. Haan, S. Haas, K. Haase, James E. Haber, N. Habermann, Faraz Hach, Syed Haider, Natsuko Hama, F. Hamdy, Anne Hamilton, M. P. Hamilton, Leng Han, G. Hanna, M. Hansmann, N. Haradhvala, O. Harismendy, Ivon Harliwong, A. Harmanci, E. Harrington, Takanori Hasegawa, D. Haussler, Steve Hawkins, S. Hayami, Shuto Hayashi, D. Hayes, S. Hayes, N. Hayward, S. Hazell, Yao He, Allison P. Heath, S. Heath, D. Hedley, A. Hegde
602 1. 2. 2020.

Patterns of somatic structural variation in human cancer genomes

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1–7. Here we develop methods to group, classify and describe somatic structural variants, using data from 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 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act. Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.


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