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(Philip\040J\056\040Stephens\054\040Patrick\040S\056\040Tarpey\054\040Helen\040Davies\054\040Peter\040Van\040Loo\054\040Peter\040Van\040Loo\054\040Christopher\040Greenman\054\040Christopher\040Greenman\054\040David\040C\056\040Wedge\054\040Serena\040Nik\055Zainal\054\040Sancha\040Martin\054\040Ignacio\040Varela\054\040Graham\040R\056\040Bignell\054\040Lucy\040R\056\040Yates\054\040Lucy\040R\056\040Yates\054\040Elli\040Papaemmanuil\054\040David\040Beare\054\040Adam\040Butler\054\040Angela\040Cheverton\054\040John\040Gamble\054\040Jonathan\040Hinton\054\040Mingming\040Jia\054\040Alagu\040Jayakumar\054\040David\040Jones\054\040Calli\040Latimer\054\040King\040Wai\040Lau\054\040Stuart\040McLaren\054\040David\040J\056\040McBride\054\040Andrew\040Menzies\054\040L\056\040Mudie\054\040Keiran\040Raine\054\040Roland\040Rad\054\040Michael\040Spencer\040Chapman\054\040Jon\040W\056\040Teague\054\040Douglas\040F\056\040Easton\054\040Anita\040Langerd\054\040Ming\040Ta\040Michael\040Lee\054\040Chen\055Yang\040Shen\054\040Benita\040Tan\040Kiat\040Tee\054\040Bernice\040Wong\040Huimin\054\040Annegien\040Broeks\054\040Ana\040Cristina\040Vargas\054\040Gulisa\040Turashvili\054\040John\040W\056M\056\040Martens\054\040Aquila\040Fatima\054\040Penelope\040Miron\054\040Suet\055Feung\040Chin\054\040Gilles\040Thomas\054\040Sandrine\040Boyault\054\040Odette\040Mariani\054\040Sunil\040R\056\040Lakhani\054\040Sunil\040R\056\040Lakhani\054\040Marc\040J\056\040van\040de\040Vijver\054\040Laura\040van\040\047t\040Veer\054\040John\040A\056\040Foekens\054\040Christine\040Desmedt\054\040Christos\040Sotiriou\054\040Andrew\040Tutt\054\040Carlos\040Caldas\054\040Carlos\040Caldas\054\040Jorge\040S\056\040Reis\055Filho\054\040Samuel\040Aparicio\054\040Anne\040Vincent\040Salomon\054\040Anne\040Lise\040Brresen\055Dale\054\040Anne\040Lise\040Brresen\055Dale\054\040Andrea\040L\056\040Richardson\054\040Peter\040J\056\040Campbell\054\040Peter\040J\056\040Campbell\054\040Peter\040J\056\040Campbell\054\040P\056\040Andrew\040Futreal\054\040Michael\040R\056\040Stratton) /Subject (All\040cancers\040carry\040somatic\040mutations\040in\040their\040genomes\056\040A\040subset\054\040known\040as\040driver\040mutations\054\040confer\040clonal\040selective\040advantage\040on\040cancer\040cells\040and\040are\040causally\040implicated\040in\040oncogenesis\054\040and\040the\040remainder\040are\040passenger\040mutations\056\040The\040driver\040mutations\040and\040mutational\040processes\040operative\040in\040breast\040cancer\040have\040not\040yet\040been\040comprehensively\040explored\056\040Here\040we\040examine\040the\040genomes\040of\040100\040tumours\040for\040somatic\040copy\040number\040changes\040and\040mutations\040in\040the\040coding\040exons\040of\040protein\055coding\040genes\056\040The\040number\040of\040somatic\040mutations\040varied\040markedly\040between\040individual\040tumours\056\040We\040found\040strong\040correlations\040between\040mutation\040number\054\040age\040at\040which\040cancer\040was\040diagnosed\040and\040cancer\040histological\040grade\054\040and\040observed\040multiple\040mutational\040signatures\054\040including\040one\040present\040in\040about\040ten\040per\040cent\040of\040tumours\040characterized\040by\040numerous\040mutations\040of\040cytosine\040at\040TpC\040dinucleotides\056\040Driver\040mutations\040were\040identified\040in\040several\040new\040cancer\040genes\040including\040AKT2\054\040ARID1B\054\040CASP8\054\040CDKN1B\054\040MAP3K1\054\040MAP3K13\054\040NCOR1\054\040SMARCD1\040and\040TBX3\056\040Among\040the\040100\040tumours\054\040we\040found\040driver\040mutations\040in\040at\040least\04040\040cancer\040genes\040and\04073\040different\040combinations\040of\040mutated\040cancer\040genes\056\040The\040results\040highlight\040the\040substantial\040genetic\040diversity\040underlying\040this\040common\040disease\056) /Keywords (21\040Jun\0402012\054\040Nature\054\040Somatic\040evolution\040in\040cancer\054\040Carcinogenesis\054\040Cancer\054\040Germline\040mutation\054\040Mutation\054\040Wellcome\040Trust\040Sanger\040Institute\054\040Wellcome\040Trust\054\040Katholieke\040Universiteit\040Leuven\054\040University\040of\040East\040Anglia\054\040Guy\047s\040and\040St\040Thomas\047\040NHS\040Foundation\040Trust\054\040Academia\040Sinica\054\040Singapore\040General\040Hospital\054\040Netherlands\040Cancer\040Institute\054\040University\040of\040Queensland\054\040University\040of\040British\040Columbia\054\040Erasmus\040University\040Rotterdam\054\040Harvard\040University\054\040University\040of\040Cambridge\054\040Claude\040Bernard\040University\040Lyon\0401\054\040Curie\040Institute\054\040Royal\040Brisbane\040and\040Women\047s\040Hospital\054\040University\040of\040Amsterdam\054\040Universit\040libre\040de\040Bruxelles\054\040The\040Breast\040Cancer\040Research\040Foundation\054\040Cambridge\040University\040Hospitals\040NHS\040Foundation\040Trust\054\040Oslo\040University\040Hospital) 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