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Nature. 2015 Jan 29;517(7536):576-82. doi: 10.1038/nature14129.

Comprehensive genomic characterization of head and neck squamous cell carcinomas.

Collaborators (348)

Lawrence MS, Sougnez C, Lichtenstein L, Cibulskis K, Lander E, Gabriel SB, Getz G, Ally A, Balasundaram M, Birol I, Bowlby R, Brooks D, Butterfield YS, Carlsen R, Cheng D, Chu A, Dhalla N, Guin R, Holt RA, Jones SJ, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Mungall AJ, Robertson AG, Schein JE, Sipahimalani P, Tam A, Thiessen N, Wong T, Protopopov A, Santoso N, Lee S, Parfenov M, Zhang J, Mahadeshwar HS, Tang J, Ren X, Seth S, Haseley P, Zeng D, Yang L, Xu AW, Song X, Pantazi A, Bristow CA, Hadjipanayis A, Seidman J, Chin L, Park PJ, Kucherlapati R, Akbani R, Casasent T, Liu W, Lu Y, Mills G, Motter T, Weinstein J, Diao L, Wang J, Hong Fan Y, Liu J, Wang K, Auman JT, Balu S, Bodenheimer T, Buda E, Hayes DN, Hoadley KA, Hoyle AP, Jefferys SR, Jones CD, Kimes PK, Liu Y, Marron JS, Meng S, Mieczkowski PA, Mose LE, Parker JS, Perou CM, Prins JF, Roach J, Shi Y, Simons JV, Singh D, Soloway MG, Tan D, Veluvolu U, Walter V, Waring S, Wilkerson MD, Wu J, Zhao N, Cherniack AD, Hammerman PS, Tward AD, Sekhar Pedamallu C, Saksena G, Jung J, Ojesina AI, Carter SL, Zack TI, Schumacher SE, Beroukhim R, Freeman SS, Meyerson M, Cho J, Chin L, Getz G, Noble MS, DiCara D, Zhang H, Heiman DI, Gehlenborg N, Voet D, Lin P, Frazer S, Stojanov P, Liu Y, Zou L, Kim J, Sougnez C, Gabriel SB, Lawrence MS, Muzny D, Doddapaneni H, Kovar C, Reid J, Morton D, Han Y, Hale W, Chao H, Chang K, Drummond JA, Gibbs RA, Kakkar N, Wheeler D, Xi L, Ciriello G, Ladanyi M, Lee W, Ramirez R, Sander C, Shen R, Sinha R, Weinhold N, Taylor BS, Aksoy BA, Dresdner G, Gao J, Gross B, Jacobsen A, Reva B, Schultz N, Sumer SO, Sun Y, Chan TA, Morris LG, Stuart J, Benz S, Ng S, Benz C, Yau C, Baylin SB, Cope L, Danilova L, Herman JG, Bootwalla M, Maglinte DT, Laird PW, Triche T Jr, Weisenberger DJ, Van Den Berg DJ, Agrawal N, Bishop J, Boutros PC, Bruce JP, Averett Byers L, Califano J, Carey TE, Chen Z, Cheng H, Chiosea SI, Cohen E, Diergaarde B, Egloff AM, El-Naggar AK, Ferris RL, Frederick MJ, Grandis JR, Guo Y, Haddad RI, Hammerman PS, Harris T, Hayes DN, Hui AB, Lee JJ, Lippman SM, Liu FF, McHugh JB, Myers J, Kwok Shing Ng P, Perez-Ordonez B, Pickering CR, Prystowsky M, Romkes M, Saleh AD, Sartor MA, Seethala R, Seiwert TY, Si H, Tward AD, Van Waes C, Waggott DM, Wiznerowicz M, Yarbrough WG, Zhang J, Zuo Z, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton C, Shelton T, Sherman M, Yena P, Black AD, Bowen J, Frick J, Gastier-Foster JM, Harper HA, Leraas K, Lichtenberg TM, Ramirez NC, Wise L, Zmuda E, Baboud J, Jensen MA, Kahn AB, Pihl TD, Pot DA, Srinivasan D, Walton JS, Wan Y, Burton RA, Davidsen T, Demchok JA, Eley G, Ferguson ML, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Saller C, Tarvin K, Chen C, Bollag R, Weinberger P, Golusiński W, Golusiński P, Ibbs M, Korski K, Mackiewicz A, Suchorska W, Szybiak B, Wiznerowicz M, Burnett K, Curley E, Gardner J, Mallery D, Penny R, Shelton T, Yena P, Beard C, Mitchell C, Sandusky G, Agrawal N, Ahn J, Bishop J, Califano J, Khan Z, Bruce JP, Hui AB, Irish J, Liu FF, Perez-Ordonez B, Waldron J, Boutros PC, Waggott DM, Myers J, William WN Jr, Lippman SM, Egea S, Gomez-Fernandez C, Herbert L, Bradford CR, Carey TE, Chepeha DB, Haddad AS, Jones TR, Komarck CM, Malakh M, McHugh JB, Moyer JS, Nguyen A, Peterson LA, Prince ME, Rozek LS, Sartor MA, Taylor EG, Walline HM, Wolf GT, Boice L, Chera BS, Funkhouser WK, Gulley ML, Hackman TG, Hayes DN, Hayward MC, Huang M, Rathmell WK, Salazar AH, Shockley WW, Shores CG, Thorne L, Weissler MC, Wrenn S, Zanation AM, Chiosea SI, Diergaarde B, Egloff AM, Ferris RL, Romkes M, Seethala R, Brown BT, Guo Y, Pham M, Yarbrough WG.

Abstract

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.

PMID:
25631445
PMCID:
PMC4311405
DOI:
10.1038/nature14129
[Indexed for MEDLINE]
Free PMC Article

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