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Nature. 2020 Feb;578(7793):82-93. doi: 10.1038/s41586-020-1969-6. Epub 2020 Feb 5.

Pan-cancer analysis of whole genomes.

Collaborators (1341)

Campbell PJ, Getz G, Korbel JO, Stuart JM, Jennings JL, Stein LD, Perry MD, Nahal-Bose HK, Ouellette BFF, Li CH, Rheinbay E, Nielsen GP, Sgroi DC, Wu CL, Faquin WC, Deshpande V, Boutros PC, Lazar AJ, Hoadley KA, Louis DN, Dursi LJ, Yung CK, Bailey MH, Saksena G, Raine KM, Buchhalter I, Kleinheinz K, Schlesner M, Zhang J, Wang W, Wheeler DA, Ding L, Simpson JT, O'Connor BD, Yakneen S, Ellrott K, Miyoshi N, Butler AP, Royo R, Shorser SI, Vazquez M, Rausch T, Tiao G, Waszak SM, Rodriguez-Martin B, Shringarpure S, Wu DY, Demidov GM, Delaneau O, Hayashi S, Imoto S, Habermann N, Segre AV, Garrison E, Cafferkey A, Alvarez EG, Heredia-Genestar JM, Muyas F, Drechsel O, Bruzos AL, Temes J, Zamora J, Baez-Ortega A, Kim HL, Mashl RJ, Ye K, DiBiase A, Huang KL, Letunic I, McLellan MD, Newhouse SJ, Shmaya T, Kumar S, Wedge DC, Wright MH, Yellapantula VD, Gerstein M, Khurana E, Marques-Bonet T, Navarro A, Bustamante CD, Siebert R, Nakagawa H, Easton DF, Ossowski S, Tubio JMC, De La Vega FM, Estivill X, Yuen D, Mihaiescu GL, Omberg L, Ferretti V, Sabarinathan R, Pich O, Gonzalez-Perez A, Taylor-Weiner A, Fittall MW, Demeulemeester J, Tarabichi M, Roberts ND, Van Loo P, Cortés-Ciriano I, Urban L, Park P, Zhu B, Pitkänen E, Li Y, Saini N, Klimczak LJ, Weischenfeldt J, Sidiropoulos N, Alexandrov LB, Rabionet R, Escaramis G, Bosio M, Holik AZ, Susak H, Prasad A, Erkek S, Calabrese C, Raeder B, Harrington E, Mayes S, Turner D, Juul S, Roberts SA, Song L, Koster R, Mirabello L, Hua X, Tanskanen TJ, Tojo M, Chen J, Aaltonen LA, Rätsch G, Schwarz RF, Butte AJ, Brazma A, Chanock SJ, Chatterjee N, Stegle O, Harismendy O, Bova GS, Gordenin DA, Haan D, Sieverling L, Feuerbach L, Chalmers D, Joly Y, Knoppers B, Molnár-Gábor F, Phillips M, Thorogood A, Townend D, Goldman M, Fonseca NA, Xiang Q, Craft B, Piñeiro-Yáñez E, Muñoz A, Petryszak R, Füllgrabe A, Al-Shahrour F, Keays M, Haussler D, Weinstein J, Huber W, Valencia A, Papatheodorou I, Zhu J, Fan Y, Torrents D, Bieg M, Chen K, Chong Z, Cibulskis K, Eils R, Fulton RS, Gelpi JL, Gonzalez S, Gut IG, Hach F, Heinold M, Hu T, Huang V, Hutter B, Jäger N, Jung J, Kumar Y, Lalansingh C, Leshchiner I, Livitz D, Ma EZ, Maruvka YE, Milovanovic A, Nielsen MM, Paramasivam N, Pedersen JS, Puiggròs M, Sahinalp SC, Sarrafi I, Stewart C, Stobbe MD, Wala JA, Wang J, Wendl M, Werner J, Wu Z, Xue H, Yamaguchi TN, Yellapantula V, Davis-Dusenbery BN, Grossman RL, Kim Y, Heinold MC, Hinton J, Jones DR, Menzies A, Stebbings L, Hess JM, Rosenberg M, Dunford AJ, Gupta M, Imielinski M, Meyerson M, Beroukhim R, Reimand J, Dhingra P, Favero F, Dentro S, Wintersinger J, Rudneva V, Park JW, Hong EP, Heo SG, Kahles A, Lehmann KV, Soulette CM, Shiraishi Y, Liu F, He Y, Demircioğlu D, Davidson NR, Greger L, Li S, Liu D, Stark SG, Zhang F, Amin SB, Bailey P, Chateigner A, Frenkel-Morgenstern M, Hou Y, Huska MR, Kilpinen H, Lamaze FC, Li C, Li X, Li X, Liu X, Marin MG, Markowski J, Nandi T, Ojesina AI, Pan-Hammarström Q, Park PJ, Pedamallu CS, Su H, Tan P, Teh BT, Wang J, Xiong H, Ye C, Yung C, Zhang X, Zheng L, Zhu S, Awadalla P, Creighton CJ, Wu K, Yang H, Göke J, Zhang Z, Brooks AN, Fittall MW, Martincorena I, Rubio-Perez C, Juul M, Schumacher S, Shapira O, Tamborero D, Mularoni L, Hornshøj H, Deu-Pons J, Muiños F, Bertl J, Guo Q, Gonzalez-Perez A, Xiang Q, Bazant W, Barrera E, Al-Sedairy ST, Aretz A, Bell C, Betancourt M, Buchholz C, Calvo F, Chomienne C, Dunn M, Edmonds S, Green E, Gupta S, Hutter CM, Jegalian K, Jones N, Lu Y, Nakagama H, Nettekoven G, Planko L, Scott D, Shibata T, Shimizu K, Stratton MR, Yugawa T, Tortora G, VijayRaghavan K, Zenklusen JC, Townend D, Knoppers BM, Aminou B, Bartolome J, Boroevich KA, Boyce R, Buchanan A, Byrne NJ, Chen Z, Cho S, Choi W, Clapham P, Dow MT, Dursi LJ, Eils J, Farcas C, Fayzullaev N, Flicek P, Heath AP, Hofmann O, Hong JH, Hudson TJ, Hübschmann D, Ivkovic S, Jeon SH, Jiao W, Kabbe R, Kahles A, Kerssemakers JNA, Kim H, Kim J, Koscher M, Koures A, Kovacevic M, Lawerenz C, Liu J, Mijalkovic S, Mijalkovic-Lazic AM, Miyano S, Nastic M, Nicholson J, Ocana D, Ohi K, Ohno-Machado L, Pihl TD, Prinz M, Radovic P, Short C, Sofia HJ, Spring J, Struck AJ, Tijanic N, Vicente D, Wang Z, Williams A, Woo Y, Wright AJ, Yang L, Hamilton MP, Johnson TA, Kahraman A, Kellis M, Polak P, Sallari R, Sinnott-Armstrong N, von Mering C, Beltran S, Gerhard DS, Gut M, Trotta JR, Whalley JP, Niu B, Espiritu SMG, Gao S, Huang Y, Lalansingh CM, Teague JW, Wendl MC, Abascal F, Bader GD, Bandopadhayay P, Barenboim J, Brunak S, Carlevaro-Fita J, Chakravarty D, Chan CWY, Choi JK, Diamanti K, Fink JL, Frigola J, Gambacorti-Passerini C, Garsed DW, Haradhvala NJ, Harmanci AO, Helmy M, Herrmann C, Hobolth A, Hodzic E, Hong C, Isaev K, Izarzugaza JMG, Johnson R, Juul RI, Kim J, Kim JK, Jan Komorowski, Lanzós A, Larsson E, Lee D, Li S, Li X, Lin Z, Liu EM, Lochovsky L, Lou S, Madsen T, Marchal K, Martinez-Fundichely A, McGillivray PD, Meyerson W, Paczkowska M, Park K, Park K, Pons T, Pulido-Tamayo S, Reyes-Salazar I, Reyna MA, Rubin MA, Salichos L, Sander C, Schumacher SE, Shackleton M, Shen C, Shrestha R, Shuai S, Tsunoda T, Umer HM, Uusküla-Reimand L, Verbeke LPC, Wadelius C, Wadi L, Warrell J, Wu G, Yu J, Zhang J, Zhang X, Zhang Y, Zhao Z, Zou L, Lawrence MS, Raphael BJ, Bailey PJ, Craft D, Goldman MJ, Aburatani H, Binder H, Dinh HQ, Heath SC, Hoffmann S, Imbusch CD, Kretzmer H, Laird PW, Martin-Subero JI, Nagae G, Shen H, Wang Q, Weichenhan D, Zhou W, Berman BP, Brors B, Plass C, Akdemir KC, Bowtell DDL, Burns KH, Busanovich J, Chan K, Dueso-Barroso A, Edwards PA, Etemadmoghadam D, Haber JE, Jones DTW, Ju YS, Kazanov MD, Koh Y, Kumar K, Lee EA, Lee JJ, Lynch AG, Macintyre G, Markowetz F, Navarro FCP, Pearson JV, Rippe K, Scully R, Villasante I, Waddell N, Yang L, Yao X, Yoon SS, Zhang CZ, Bergstrom EN, Boot A, Covington K, Fujimoto A, Huang MN, Islam SMA, McPherson JR, Morganella S, Mustonen V, Ng AWT, Prokopec SD, Vázquez-García I, Wu Y, Yousif F, Yu W, Rozen SG, Rudneva VA, Shringarpure SS, Turner DJ, Xia T, Atwal G, Chang DK, Cooke SL, Faltas BM, Haider S, Kaiser VB, Karlić R, Kato M, Kübler K, Margolin A, Martin S, Nik-Zainal S, P'ng C, Semple CA, Smith J, Sun RX, Thai K, Wright DW, Yuan K, Biankin AV, Garraway L, Grimmond SM, Adams DJ, Anur P, Cao S, Christie EL, Cmero M, Cun Y, Dawson KJ, Dentro SC, Deshwar AG, Donmez N, Drews RM, Gerstung M, Ha G, Haase K, Jerman L, Ji Y, Jolly C, Lee J, Lee-Six H, Malikic S, Mitchell TJ, Morris QD, Oesper L, Peifer M, Peto M, Rosebrock D, Rubanova Y, Salcedo A, Sengupta S, Shi R, Shin SJ, Spiro O, Vembu S, Wintersinger JA, Yang TP, Yu K, Zhu H, Spellman PT, Weinstein JN, Chen Y, Fujita M, Han L, Hasegawa T, Komura M, Li J, Mizuno S, Shimizu E, Wang Y, Xu Y, Yamaguchi R, Yang F, Yang Y, Yoon CJ, Yuan Y, Liang H, Alawi M, Borozan I, Brewer DS, Cooper CS, Desai N, Grundhoff A, Iskar M, Su X, Zapatka M, Lichter P, Alsop K, Bruxner TJC, Christ AN, Cordner SM, Cowin PA, Drapkin R, Fereday S, George J, Hamilton A, Holmes O, Hung JA, Kassahn KS, Kazakoff SH, Kennedy CJ, Leonard CR, Mileshkin L, Miller DK, Arnau GM, Mitchell C, Newell F, Nones K, Patch AM, Quinn MC, Taylor DF, Thorne H, Traficante N, Vedururu R, Waddell NM, Waring PM, Wood S, Xu Q, deFazio A, Anderson MJ, Antonello D, Barbour AP, Bassi C, Bersani S, Cataldo I, Chantrill LA, Chiew YE, Chou A, Cingarlini S, Cloonan N, Corbo V, Davi MV, Duthie FR, Gill AJ, Graham JS, Harliwong I, Jamieson NB, Johns AL, Kench JG, Landoni L, Lawlor RT, Mafficini A, Merrett ND, Miotto M, Musgrove EA, Nagrial AM, Oien KA, Pajic M, Pinese M, Robertson AJ, Rooman I, Rusev BC, Samra JS, Scardoni M, Scarlett CJ, Scarpa A, Sereni E, Sikora KO, Simbolo M, Taschuk ML, Toon CW, Vicentini C, Wu J, Zeps N, Behren A, Burke H, Cebon J, Dagg RA, De Paoli-Iseppi R, Dutton-Regester K, Field MA, Fitzgerald A, Hersey P, Jakrot V, Johansson PA, Kakavand H, Kefford RF, Lau LMS, Long GV, Pickett HA, Pritchard AL, Pupo GM, Saw RPM, Schramm SJ, Shang CA, Shang P, Spillane AJ, Stretch JR, Tembe V, Thompson JF, Vilain RE, Wilmott JS, Yang JY, Hayward NK, Mann GJ, Scolyer RA, Bartlett J, Bavi P, Chadwick DE, Chan-Seng-Yue M, Cleary S, Connor AA, Czajka K, Denroche RE, Dhani NC, Eagles J, Gallinger S, Grant RC, Hedley D, Hollingsworth MA, Jang GH, Johns J, Kalimuthu S, Liang SB, Lungu I, Luo X, Mbabaali F, McPherson TA, Miller JK, Moore MJ, Notta F, Pasternack D, Petersen GM, Roehrl MHA, Sam M, Selander I, Serra S, Shahabi S, Thayer SP, Timms LE, Wilson GW, Wilson JM, Wouters BG, McPherson JD, Beck TA, Bhandari V, Collins CC, Fleshner NE, Fox NS, Fraser M, Heisler LE, Lalonde E, Livingstone J, Meng A, Sabelnykova VY, Shiah YJ, Van der Kwast T, Bristow RG, Ding S, Fan D, Li L, Nie Y, Xiao X, Xing R, Yang S, Yu Y, Zhou Y, Banks RE, Bourque G, Brennan P, Letourneau L, Riazalhosseini Y, Scelo G, Vasudev N, Viksna J, Lathrop M, Tost J, Ahn SM, Aparicio S, Arnould L, Aure MR, Bhosle SG, Birney E, Borg A, Boyault S, Brinkman AB, Brock JE, Broeks A, Børresen-Dale AL, Caldas C, Chin SF, Davies H, Desmedt C, Dirix L, Dronov S, Ehinger A, Eyfjord JE, Fatima A, Foekens JA, Futreal PA, Garred Ø, Giri DD, Glodzik D, Grabau D, Hilmarsdottir H, Hooijer GK, Jacquemier J, Jang SJ, Jonasson JG, Jonkers J, Kim HY, King TA, Knappskog S, Kong G, Krishnamurthy S, Lakhani SR, Langerød A, Larsimont D, Lee HJ, Lee JY, Lee MTM, Lingjærde OC, MacGrogan G, Martens JWM, O'Meara S, Pauporté I, Pinder S, Pivot X, Provenzano E, Purdie CA, Ramakrishna M, Ramakrishnan K, Reis-Filho J, Richardson AL, Ringnér M, Rodriguez JB, Rodríguez-González FG, Romieu G, Salgado R, Sauer T, Shepherd R, Sieuwerts AM, Simpson PT, Smid M, Sotiriou C, Span PN, Stefánsson ÓA, Stenhouse A, Stunnenberg HG, Sweep F, Tan BKT, Thomas G, Thompson AM, Tommasi S, Treilleux I, Tutt A, Ueno NT, Van Laere S, Van den Eynden GG, Vermeulen P, Viari A, Vincent-Salomon A, Wong BH, Yates L, Zou X, van Deurzen CHM, van de Vijver MJ, Van't Veer L, Ammerpohl O, Aukema S, Bergmann AK, Bernhart SH, Borkhardt A, Borst C, Burkhardt B, Claviez A, Goebler ME, Haake A, Haas S, Hansmann M, Hoell JI, Hummel M, Karsch D, Klapper W, Kneba M, Kreuz M, Kube D, Küppers R, Lenze D, Loeffler M, López C, Mantovani-Löffler L, Möller P, Ott G, Radlwimmer B, Richter J, Rohde M, Rosenstiel PC, Rosenwald A, Schilhabel MB, Schreiber S, Stadler PF, Staib P, Stilgenbauer S, Sungalee S, Szczepanowski M, Toprak UH, Trümper LHP, Wagener R, Zenz T, Hovestadt V, von Kalle C, Kool M, Korshunov A, Landgraf P, Lehrach H, Northcott PA, Pfister SM, Reifenberger G, Warnatz HJ, Wolf S, Yaspo ML, Assenov Y, Gerhauser C, Minner S, Schlomm T, Simon R, Sauter G, Sültmann H, Biswas NK, Maitra A, Majumder PP, Sarin R, Barbi S, Bonizzato G, Cantù C, Dei Tos AP, Fassan M, Grimaldi S, Luchini C, Malleo G, Marchegiani G, Milella M, Paiella S, Pea A, Pederzoli P, Ruzzenente A, Salvia R, Sperandio N, Arai Y, Hama N, Hiraoka N, Hosoda F, Nakamura H, Ojima H, Okusaka T, Totoki Y, Urushidate T, Fukayama M, Ishikawa S, Katai H, Katoh H, Komura D, Rokutan H, Saito-Adachi M, Suzuki A, Taniguchi H, Tatsuno K, Ushiku T, Yachida S, Yamamoto S, Aikata H, Arihiro K, Ariizumi SI, Chayama K, Furuta M, Gotoh K, Hayami S, Hirano S, Kawakami Y, Maejima K, Nakamura T, Nakano K, Ohdan H, Sasaki-Oku A, Tanaka H, Ueno M, Yamamoto M, Yamaue H, Choo SP, Cutcutache I, Khuntikeo N, Ong CK, Pairojkul C, Popescu I, Ahn KS, Aymerich M, Lopez-Guillermo A, López-Otín C, Puente XS, Campo E, Amary F, Baumhoer D, Behjati S, Bjerkehagen B, Futreal PA, Myklebost O, Pillay N, Tarpey P, Tirabosco R, Zaikova O, Flanagan AM, Boultwood J, Bowen DT, Cazzola M, Green AR, Hellstrom-Lindberg E, Malcovati L, Nangalia J, Papaemmanuil E, Vyas P, Ang Y, Barr H, Beardsmore D, Eldridge M, Gossage J, Grehan N, Hanna GB, Hayes SJ, Hupp TR, Khoo D, Lagergren J, Lovat LB, MacRae S, O'Donovan M, O'Neill JR, Parsons SL, Preston SR, Puig S, Roques T, Sanders G, Sothi S, Tavaré S, Tucker O, Turkington R, Underwood TJ, Welch I, Fitzgerald RC, Berney DM, De Bono JS, Cahill D, Camacho N, Dennis NM, Dudderidge T, Edwards SE, Fisher C, Foster CS, Ghori M, Gill P, Gnanapragasam VJ, Gundem G, Hamdy FC, Hawkins S, Hazell S, Howat W, Isaacs WB, Karaszi K, Kay JD, Khoo V, Kote-Jarai Z, Kremeyer B, Kumar P, Lambert A, Leongamornlert DA, Livni N, Lu YJ, Luxton HJ, Marsden L, Massie CE, Matthews L, Mayer E, McDermott U, Merson S, Neal DE, Ng A, Nicol D, Ogden C, Rowe EW, Shah NC, Thomas S, Thompson A, Verrill C, Visakorpi T, Warren AY, Whitaker HC, Zhang H, van As N, Eeles RA, Abeshouse A, Agrawal N, Akbani R, Al-Ahmadie H, Albert M, Aldape K, Ally A, Appelbaum EL, Armenia J, Asa S, Auman JT, Balasundaram M, Balu S, Barnholtz-Sloan J, Bathe OF, Baylin SB, Benz C, Berchuck A, Berrios M, Bigner D, Birrer M, Bodenheimer T, Boice L, Bootwalla MS, Bosenberg M, Bowlby R, Boyd J, Broaddus RR, Brock M, Brooks D, Bullman S, Caesar-Johnson SJ, Carey TE, Carlsen R, Cerfolio R, Chandan VS, Chen HW, Cherniack AD, Chien J, Cho J, Chuah E, Cibulskis C, Cope L, Cordes MG, 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Abstract

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10-18.

PMID:
32025007
PMCID:
PMC7025898
[Available on 2020-08-05]
DOI:
10.1038/s41586-020-1969-6

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