TY - JOUR
T1 - Comprehensive genomic characterization of head and neck squamous cell carcinomas
AU - Lawrence, Michael S.
AU - Sougnez, Carrie
AU - Lichtenstein, Lee
AU - Cibulskis, Kristian
AU - Lander, Eric
AU - Gabriel, Stacey B.
AU - Getz, Gad
AU - Ally, Adrian
AU - Balasundaram, Miruna
AU - Birol, Inanc
AU - Bowlby, Reanne
AU - Brooks, Denise
AU - Butterfield, Yaron S.N.
AU - Carlsen, Rebecca
AU - Cheng, Dean
AU - Chu, Andy
AU - Dhalla, Noreen
AU - Guin, Ranabir
AU - Holt, Robert A.
AU - Jones, Steven J.M.
AU - Lee, Darlene
AU - Li, Haiyan I.
AU - Marra, Marco A.
AU - Mayo, Michael
AU - Moore, Richard A.
AU - Mungall, Andrew J.
AU - Robertson, A. Gordon
AU - Schein, Jacqueline E.
AU - Sipahimalani, Payal
AU - Tam, Angela
AU - Thiessen, Nina
AU - Wong, Tina
AU - Protopopov, Alexei
AU - Santoso, Netty
AU - Lee, Semin
AU - Parfenov, Michael
AU - Zhang, Jianhua
AU - Mahadeshwar, Harshad S.
AU - Tang, Jiabin
AU - Ren, Xiaojia
AU - Seth, Sahil
AU - Haseley, Psalm
AU - Zeng, Dong
AU - Yang, Lixing
AU - Xu, Andrew W.
AU - Song, Xingzhi
AU - Pantazi, Angeliki
AU - Bristow, Christopher A.
AU - Hadjipanayis, Angela
AU - Liu, Jinze
N1 - Funding Information:
Acknowledgements This study was supported by National Institutes of Health (NIH) grants: P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025 and RO1 CA 095419. Supported by The Bobby F. Garrett Fund for Head and Neck Cancer Research and NIDCD Intramural Projects ZIA-DC-000016, 73 and 74.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/1/29
Y1 - 2015/1/29
N2 - 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.
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.
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U2 - 10.1038/nature14129
DO - 10.1038/nature14129
M3 - Article
C2 - 25631445
AN - SCOPUS:84923197605
VL - 517
SP - 576
EP - 582
IS - 7536
ER -
