The repertoire of mutational signatures in human cancer
Creators: name: Alexandrov, Ludmil B
name: Kim, Jaegil
name: Haradhvala, Nicholas J
name: Huang, Mi Ni
name: Ng, Alvin Wei Tian
name: Wu, Yang
name: Boot, Arnoud
name: Covington, Kyle R
name: Gordenin, Dmitry A
name: Bergstrom, Erik N
name: Islam, SM Ashiqul
name: Lopez-Bigas, Nuria
name: Klimczak, Leszek J
name: McPherson, John R
name: Morganella, Sandro
name: Sabarinathan, Radhakrishnan
name: Wheeler, David A
name: Mustonen, Ville
name: Boutros, Paul
name: Chan, Kin
name: Fujimoto, Akihiro
name: Getz, Gad
name: Kazanov, Marat
name: Lawrence, Michael
name: Martincorena, Iñigo
name: Nakagawa, Hidewaki
name: Polak, Paz
name: Prokopec, Stephenie
name: Roberts, Steven A
name: Rozen, Steven G
name: Saini, Natalie
name: Shibata, Tatsuhiro
name: Shiraishi, Yuichi
name: Stratton, Michael R
name: Teh, Bin Tean
name: Vázquez-García, Ignacio
name: Yousif, Fouad
name: Yu, Willie
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: Akdemir, Kadir C
name: Al-Ahmadie, Hikmat
name: Al-Sedairy, Sultan T
name: Al-Shahrour, Fatima
name: Alawi, Malik
name: Albert, Monique
name: Aldape, Kenneth
name: Ally, Adrian
name: Alsop, Kathryn
name: Alvarez, Eva G
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: Baez-Ortega, Adrian
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: Berman, Benjamin P
name: Berney, Daniel M
name: Bernhart, Stephan H
name: Beroukhim, Rameen
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: 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: Boutros, Paul C
name: Bova, G Steven
name: Bowen, David T
name: Bowlby, Reanne
name: Bowtell, David DL
name: Boyault, Sandrine
name: Boyce, Rich
name: Boyd, Jeffrey
name: Brazma, Alvis
name: Brennan, Paul
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: Brors, Benedikt
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: Burns, Kathleen H
name: Busanovich, John
name: Bustamante, Carlos D
name: Butler, Adam P
name: Butte, Atul J
name: Byrne, Niall J
name: Børresen-Dale, Anne-Lise
name: Caesar-Johnson, Samantha J
name: Cafferkey, Andy
name: Cahill, Declan
name: Calabrese, Claudia
name: Caldas, Carlos
name: Calvo, Fabien
name: Camacho, Niedzica
name: Campbell, Peter J
name: Campo, Elias
name: Cantù, Cinzia
name: Cao, Shaolong
name: Carey, Thomas E
name: Carlevaro-Fita, Joana
name: Carlsen, Rebecca
name: Cataldo, Ivana
name: Cazzola, Mario
name: Cebon, Jonathan
name: Cerfolio, Robert
name: Chadwick, Dianne E
name: Chakravarty, Dimple
name: Chalmers, Don
name: Chan, Calvin Wing Yiu
name: Chan-Seng-Yue, Michelle
name: Chandan, Vishal S
name: Chang, David K
name: Chanock, Stephen J
name: Chantrill, Lorraine A
name: Chateigner, Aurélien
name: Chatterjee, Nilanjan
name: Chayama, Kazuaki
name: Chen, Hsiao-Wei
name: Chen, Jieming
name: Chen, Ken
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
name: Choi, Jung Kyoon
name: Choi, Wan
name: Chomienne, Christine
name: Chong, Zechen
name: Choo, Su Pin
name: Chou, Angela
name: Christ, Angelika N
name: Christie, Elizabeth L
name: Chuah, Eric
name: Cibulskis, Carrie
name: Cibulskis, Kristian
name: Cingarlini, Sara
name: Clapham, Peter
name: Claviez, Alexander
name: Cleary, Sean
name: Cloonan, Nicole
name: Cmero, Marek
name: Collins, Colin C
name: Connor, Ashton A
name: Cooke, Susanna L
name: Cooper, Colin S
name: Cope, Leslie
name: Corbo, Vincenzo
name: Cordes, Matthew G
name: Cordner, Stephen M
name: Cortés-Ciriano, Isidro
name: Covington, Kyle
name: Cowin, Prue A
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
name: Dagg, Rebecca A
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
name: Demchok, John A
name: Demeulemeester, Jonas
name: Demidov, German M
name: Demircioğlu, Deniz
name: Dennis, Nening M
name: Denroche, Robert E
name: Dentro, Stefan C
name: Desai, Nikita
name: Deshpande, Vikram
name: Deshwar, Amit G
name: Desmedt, Christine
name: Deu-Pons, Jordi
name: Dhalla, Noreen
name: Dhani, Neesha C
name: Dhingra, Priyanka
name: Dhir, Rajiv
name: DiBiase, Anthony
name: Diamanti, Klev
name: Ding, Li
name: Ding, Shuai
name: Dinh, Huy Q
name: Dirix, Luc
name: Doddapaneni, HarshaVardhan
name: Donmez, Nilgun
name: Dow, Michelle T
name: Drapkin, Ronny
name: Drechsel, Oliver
name: Drews, Ruben M
name: Serge, Serge
name: Dudderidge, Tim
name: Dueso-Barroso, Ana
name: Dunford, Andrew J
name: Dunn, Michael
name: Dursi, Lewis Jonathan
name: Duthie, Fraser R
name: Dutton-Regester, Ken
name: Eagles, Jenna
name: Easton, Douglas F
name: Edmonds, Stuart
name: Edwards, Paul A
name: Edwards, Sandra E
name: Eeles, Rosalind A
name: Ehinger, Anna
name: Eils, Juergen
name: Eils, Roland
name: El-Naggar, Adel
name: Eldridge, Matthew
name: Ellrott, Kyle
name: Erkek, Serap
name: Escaramis, Georgia
name: Espiritu, Shadrielle MG
name: Estivill, Xavier
name: Etemadmoghadam, Dariush
name: Eyfjord, Jorunn E
name: Faltas, Bishoy M
name: Fan, Daiming
name: Fan, Yu
name: Faquin, William C
name: Farcas, Claudiu
name: Fassan, Matteo
name: Fatima, Aquila
name: Favero, Francesco
name: Fayzullaev, Nodirjon
name: Felau, Ina
name: Fereday, Sian
name: Ferguson, Martin L
name: Ferretti, Vincent
name: Feuerbach, Lars
name: Field, Matthew A
name: Fink, J Lynn
name: Finocchiaro, Gaetano
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name: Fittall, Matthew W
name: Fitzgerald, Anna
name: Fitzgerald, Rebecca C
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name: Fleshner, Neil E
name: Flicek, Paul
name: Foekens, John A
name: Fong, Kwun M
name: Fonseca, Nuno A
name: Foster, Christopher S
name: Fox, Natalie S
name: Fraser, Michael
name: Frazer, Scott
name: Frenkel-Morgenstern, Milana
name: Friedman, William
name: Frigola, Joan
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name: Fujita, Masashi
name: Fukayama, Masashi
name: Fulton, Lucinda A
name: Fulton, Robert S
name: Furuta, Mayuko
name: Futreal, P Andrew
name: Füllgrabe, Anja
name: Gabriel, Stacey B
name: Gallinger, Steven
name: Gambacorti-Passerini, Carlo
name: Gao, Jianjiong
name: Gao, Shengjie
name: Garraway, Levi
name: Garred, Øystein
name: Garrison, Erik
name: Garsed, Dale W
name: Gehlenborg, Nils
name: Gelpi, Josep LL
name: George, Joshy
name: Gerhard, Daniela S
name: Gerhauser, Clarissa
name: Gershenwald, Jeffrey E
name: Gerstein, Mark
name: Gerstung, Moritz
name: Ghori, Mohammed
name: Ghossein, Ronald
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name: Gibbs, Richard A
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name: Gill, Pelvender
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name: Glodzik, Dominik
name: Gnanapragasam, Vincent J
name: Goebler, Maria Elisabeth
name: Goldman, Mary J
name: Gomez, Carmen
name: Gonzalez, Santiago
name: Gonzalez-Perez, Abel
name: Gossage, James
name: Gotoh, Kunihito
name: Govindan, Ramaswamy
name: Grabau, Dorthe
name: Graham, Janet S
name: Grant, Robert C
name: Green, Anthony R
name: Green, Eric
name: Greger, Liliana
name: Grehan, Nicola
name: Grimaldi, Sonia
name: Grimmond, Sean M
name: Grossman, Robert L
name: Grundhoff, Adam
name: Gundem, Gunes
name: Guo, Qianyun
name: Gupta, Manaswi
name: Gupta, Shailja
name: Gut, Ivo G
name: Gut, Marta
name: Göke, Jonathan
name: Ha, Gavin
name: Haake, Andrea
name: Haan, David
name: Haas, Siegfried
name: Haase, Kerstin
name: Haber, James E
name: Habermann, Nina
name: Hach, Faraz
name: Haider, Syed
name: Hama, Natsuko
name: Hamdy, Freddie C
name: Hamilton, Anne
name: Hamilton, Mark P
name: Han, Leng
name: Hanna, George B
name: Hansmann, Martin
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name: Harmanci, Arif O
name: Harrington, Eoghan
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name: Hayes, D Neil
name: Hayes, Stephen J
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name: Hellstrom-Lindberg, Eva
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name: Heredia-Genestar, José María
name: Herrmann, Carl
name: Hersey, Peter
name: Hess, Julian M
name: Hilmarsdottir, Holmfridur
name: Hinton, Jonathan
name: Hirano, Satoshi
name: Hiraoka, Nobuyoshi
name: Hoadley, Katherine A
name: Hobolth, Asger
name: Hodzic, Ermin
name: Hoell, Jessica I
name: Hoffmann, Steve
name: Hofmann, Oliver
name: Holbrook, Andrea
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name: Hollingsworth, Michael A
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name: Hong, Eun Pyo
name: Hong, Jongwhi H
name: Hooijer, Gerrit K
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name: Hosoda, Fumie
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name: Hovestadt, Volker
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name: Hu, Jianhong
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name: Huang, Mei
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name: Hudson, Thomas J
name: Hummel, Michael
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name: Iacobuzio-Donahue, Christine A
name: Imbusch, Charles David
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name: Imoto, Seiya
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name: Isaev, Keren
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name: Ivkovic, Sinisa
name: Izarzugaza, Jose MG
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name: Jakrot, Valerie
name: Jamieson, Nigel B
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name: Jang, Se Jin
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name: Jefferys, Stuart R
name: Jegalian, Karine
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name: Jeon, Seung-Hyup
name: Jerman, Lara
name: Ji, Yuan
name: Jiao, Wei
name: Johansson, Peter A
name: Johns, Amber L
name: Johns, Jeremy
name: Johnson, Rory
name: Johnson, Todd A
name: Jolly, Clemency
name: Joly, Yann
name: Jonasson, Jon G
name: Jones, Corbin D
name: Jones, David R
name: Jones, David TW
name: Jones, Nic
name: Jones, Steven JM
name: Jonkers, Jos
name: Ju, Young Seok
name: Juhl, Hartmut
name: Jung, Jongsun
name: Juul, Malene
name: Juul, Randi Istrup
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name: Jäger, Natalie
name: Kabbe, Rolf
name: Kahles, Andre
name: Kahraman, Abdullah
name: Kaiser, Vera B
name: Kakavand, Hojabr
name: Kalimuthu, Sangeetha
name: von Kalle, Christof
name: Kang, Koo Jeong
name: Karaszi, Katalin
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name: Karlić, Rosa
name: Karsch, Dennis
name: Kasaian, Katayoon
name: Kassahn, Karin S
name: Katai, Hitoshi
name: Kato, Mamoru
name: Katoh, Hiroto
name: Kawakami, Yoshiiku
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name: Kazakoff, Stephen H
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name: Kim, Hyung-Yong
name: Kim, Hyunghwan
name: Kim, Jihoon
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name: Kim, Youngwook
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name: Korchina, Viktoriya
name: Korshunov, Andrey
name: Koscher, Michael
name: Koster, Roelof
name: Kote-Jarai, Zsofia
name: Koures, Antonios
name: Kovacevic, Milena
name: Kremeyer, Barbara
name: Kretzmer, Helene
name: Kreuz, Markus
name: Krishnamurthy, Savitri
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name: Miotto, Marco
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name: Molnár-Gábor, Fruzsina
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name: Nielsen, G Petur
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name: Nones, Katia
name: Northcott, Paul A
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name: O’Neill, J Robert
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name: Ohdan, Hideki
name: Ohi, Kazuhiro
name: Ohno-Machado, Lucila
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name: Zheng, Xiuqing
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Publisher: name: The Francis Crick Institute
Year: 2024
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: Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3–15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.