PMID- 25631445 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20240211 IS - 1476-4687 (Electronic) IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 517 IP - 7536 DP - 2015 Jan 29 TI - Comprehensive genomic characterization of head and neck squamous cell carcinomas. PG - 576-82 LID - 10.1038/nature14129 [doi] AB - The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs. CN - Cancer Genome Atlas Network LA - eng GR - UL1 TR000433/TR/NCATS NIH HHS/United States GR - U24 CA143882/CA/NCI NIH HHS/United States GR - K08 DE024774/DE/NIDCR NIH HHS/United States GR - U24 CA143843/CA/NCI NIH HHS/United States GR - U54 HG003079/HG/NHGRI NIH HHS/United States GR - ZIA-DC-000073/DC/NIDCD NIH HHS/United States GR - U24 CA143883/CA/NCI NIH HHS/United States GR - R01 CA095419/CA/NCI NIH HHS/United States GR - U24 CA143867/CA/NCI NIH HHS/United States GR - R01 DE023685/DE/NIDCR NIH HHS/United States GR - UL1 TR000005/TR/NCATS NIH HHS/United States GR - P30 CA016672/CA/NCI NIH HHS/United States GR - ZIA DC000016/ImNIH/Intramural NIH HHS/United States GR - U54 HG003067/HG/NHGRI NIH HHS/United States GR - U24 CA143835/CA/NCI NIH HHS/United States GR - P30 CA047904/CA/NCI NIH HHS/United States GR - U24 CA143866/CA/NCI NIH HHS/United States GR - P50CA097190/CA/NCI NIH HHS/United States GR - U24 CA143845/CA/NCI NIH HHS/United States GR - U24 CA143799/CA/NCI NIH HHS/United States GR - R01 CA 095419/CA/NCI NIH HHS/United States GR - U54 HG003273/HG/NHGRI NIH HHS/United States GR - P30 CA008748/CA/NCI NIH HHS/United States GR - U24 CA144025/CA/NCI NIH HHS/United States GR - U24 CA180951/CA/NCI NIH HHS/United States GR - U24 CA143840/CA/NCI NIH HHS/United States GR - U24 CA143858/CA/NCI NIH HHS/United States GR - ZIA-DC-000074/DC/NIDCD NIH HHS/United States GR - P50CA16672/CA/NCI NIH HHS/United States GR - P30 CA177558/CA/NCI NIH HHS/United States GR - R01 HG006272/HG/NHGRI NIH HHS/United States GR - P50 CA097190/CA/NCI NIH HHS/United States GR - U24 CA143848/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (DNA, Neoplasm) RN - 0 (RNA, Neoplasm) RN - 0 (Transcription Factors) SB - IM MH - Carcinoma, Squamous Cell/*genetics MH - DNA Copy Number Variations/genetics MH - DNA, Neoplasm/genetics MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - Genome, Human/*genetics MH - *Genomics MH - Head and Neck Neoplasms/*genetics MH - Humans MH - Male MH - Molecular Targeted Therapy MH - Mutation/genetics MH - Oncogenes/genetics MH - RNA, Neoplasm/genetics MH - Signal Transduction/genetics MH - Squamous Cell Carcinoma of Head and Neck MH - Transcription Factors/metabolism PMC - PMC4311405 MID - NIHMS646209 COIS- The author declare no competing financial interests. FIR - Lawrence, Michael S IR - Lawrence MS FIR - Sougnez, Carrie IR - Sougnez C FIR - Lichtenstein, Lee IR - Lichtenstein L FIR - Cibulskis, Kristian IR - Cibulskis K FIR - Lander, Eric IR - Lander E FIR - Gabriel, Stacey B IR - Gabriel SB FIR - Getz, Gad IR - Getz G FIR - Ally, Adrian IR - Ally A FIR - Balasundaram, Miruna IR - Balasundaram M FIR - Birol, Inanc IR - Birol I FIR - Bowlby, Reanne IR - Bowlby R FIR - Brooks, Denise IR - Brooks D FIR - Butterfield, Yaron S N IR - Butterfield YS FIR - Carlsen, Rebecca IR - Carlsen R FIR - Cheng, Dean IR - Cheng D FIR - Chu, Andy IR - Chu A FIR - Dhalla, Noreen IR - Dhalla N FIR - Guin, Ranabir IR - Guin R FIR - Holt, Robert A IR - Holt RA FIR - Jones, Steven J M IR - Jones SJ FIR - Lee, Darlene IR - Lee D FIR - Li, Haiyan I IR - Li HI FIR - Marra, Marco A IR - Marra MA FIR - Mayo, Michael IR - Mayo M FIR - Moore, Richard A IR - Moore RA FIR - Mungall, Andrew J IR - Mungall AJ FIR - Robertson, A Gordon IR - Robertson AG FIR - Schein, Jacqueline E IR - 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Mallery, David IR - Mallery D FIR - Morris, Scott IR - Morris S FIR - Paulauskis, Joseph IR - Paulauskis J FIR - Penny, Robert IR - Penny R FIR - Shelton, Candace IR - Shelton C FIR - Shelton, Troy IR - Shelton T FIR - Sherman, Mark IR - Sherman M FIR - Yena, Peggy IR - Yena P FIR - Black, Aaron D IR - Black AD FIR - Bowen, Jay IR - Bowen J FIR - Frick, Jessica IR - Frick J FIR - Gastier-Foster, Julie M IR - Gastier-Foster JM FIR - Harper, Hollie A IR - Harper HA FIR - Leraas, Kristen IR - Leraas K FIR - Lichtenberg, Tara M IR - Lichtenberg TM FIR - Ramirez, Nilsa C IR - Ramirez NC FIR - Wise, Lisa IR - Wise L FIR - Zmuda, Erik IR - Zmuda E FIR - Baboud, Julien IR - Baboud J FIR - Jensen, Mark A IR - Jensen MA FIR - Kahn, Ari B IR - Kahn AB FIR - Pihl, Todd D IR - Pihl TD FIR - Pot, David A IR - Pot DA FIR - Srinivasan, Deepak IR - Srinivasan D FIR - Walton, Jessica S IR - Walton JS FIR - Wan, Yunhu IR - Wan Y FIR - Burton, Robert A IR - Burton RA FIR - Davidsen, Tanja IR - Davidsen T FIR - 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Gardner J FIR - Mallery, David IR - Mallery D FIR - Penny, Robert IR - Penny R FIR - Shelton, Troy IR - Shelton T FIR - Yena, Peggy IR - Yena P FIR - Beard, Christina IR - Beard C FIR - Mitchell, Colleen IR - Mitchell C FIR - Sandusky, George IR - Sandusky G FIR - Agrawal, Nishant IR - Agrawal N FIR - Ahn, Julie IR - Ahn J FIR - Bishop, Justin IR - Bishop J FIR - Califano, Joseph IR - Califano J FIR - Khan, Zubair IR - Khan Z FIR - Bruce, Jeff P IR - Bruce JP FIR - Hui, Angela B Y IR - Hui AB FIR - Irish, Jonathan IR - Irish J FIR - Liu, Fei-Fei IR - Liu FF FIR - Perez-Ordonez, Bayardo IR - Perez-Ordonez B FIR - Waldron, John IR - Waldron J FIR - Boutros, Paul C IR - Boutros PC FIR - Waggott, Daryl M IR - Waggott DM FIR - Myers, Jeff IR - Myers J FIR - William, William N Jr IR - William WN Jr FIR - Lippman, Scott M IR - Lippman SM FIR - Egea, Sophie IR - Egea S FIR - Gomez-Fernandez, Carmen IR - Gomez-Fernandez C FIR - Herbert, Lynn IR - Herbert L FIR - Bradford, Carol R IR - Bradford CR FIR - Carey, Thomas E IR - Carey TE FIR - Chepeha, Douglas B IR - Chepeha DB FIR - Haddad, Andrea S IR - Haddad AS FIR - Jones, Tamara R IR - Jones TR FIR - Komarck, Christine M IR - Komarck CM FIR - Malakh, Mayya IR - Malakh M FIR - McHugh, Jonathan B IR - McHugh JB FIR - Moyer, Jeffrey S IR - Moyer JS FIR - Nguyen, Ariane IR - Nguyen A FIR - Peterson, Lisa A IR - Peterson LA FIR - Prince, Mark E IR - Prince ME FIR - Rozek, Laura S IR - Rozek LS FIR - Sartor, Maureen A IR - Sartor MA FIR - Taylor, Evan G IR - Taylor EG FIR - Walline, Heather M IR - Walline HM FIR - Wolf, Gregory T IR - Wolf GT FIR - Boice, Lori IR - Boice L FIR - Chera, Bhishamjit S IR - Chera BS FIR - Funkhouser, William K IR - Funkhouser WK FIR - Gulley, Margaret L IR - Gulley ML FIR - Hackman, Trevor G IR - Hackman TG FIR - Hayes, D Neil IR - Hayes DN FIR - Hayward, Michele C IR - Hayward MC FIR - Huang, Mei IR - Huang M FIR - Rathmell, W Kimryn IR - Rathmell WK FIR - Salazar, Ashley H IR - Salazar AH FIR - Shockley, William W IR - Shockley WW FIR - Shores, Carol G IR - Shores CG FIR - Thorne, Leigh IR - Thorne L FIR - Weissler, Mark C IR - Weissler MC FIR - Wrenn, Sylvia IR - Wrenn S FIR - Zanation, Adam M IR - Zanation AM FIR - Chiosea, Simion I IR - Chiosea SI FIR - Diergaarde, Brenda IR - Diergaarde B FIR - Egloff, Ann Marie IR - Egloff AM FIR - Ferris, Robert L IR - Ferris RL FIR - Romkes, Marjorie IR - Romkes M FIR - Seethala, Raja IR - Seethala R FIR - Brown, Brandee T IR - Brown BT FIR - Guo, Yan IR - Guo Y FIR - Pham, Michelle IR - Pham M FIR - Yarbrough, Wendell G IR - Yarbrough WG EDAT- 2015/01/30 06:00 MHDA- 2015/05/12 06:00 PMCR- 2015/01/28 CRDT- 2015/01/30 06:00 PHST- 2013/10/19 00:00 [received] PHST- 2014/12/01 00:00 [accepted] PHST- 2015/01/30 06:00 [entrez] PHST- 2015/01/30 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] PHST- 2015/01/28 00:00 [pmc-release] AID - nature14129 [pii] AID - BFnature14129 [pii] AID - 10.1038/nature14129 [doi] PST - ppublish SO - Nature. 2015 Jan 29;517(7536):576-82. doi: 10.1038/nature14129.