Comprehensive genomic characterization of head and neck squamous cell carcinomas

The Cancer Genome Atlas Network, Michael S. Lawrence, Carrie Sougnez, Lee Lichtenstein, Kristian Cibulskis, Eric Lander, Stacey B. Gabriel, Gad Getz, Adrian Ally, Miruna Balasundaram, Inanc Birol, Reanne Bowlby, Denise Brooks, Yaron S.N. Butterfield, Rebecca Carlsen, Dean Cheng, Andy Chu, Noreen Dhalla, Ranabir Guin, Robert A. Holt & 31 others Steven J.M. Jones, Darlene Lee, Haiyan I. Li, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, A. Gordon Robertson, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Tina Wong, Netty Santoso, Semin Lee, Michael Parfenov, Jianhua Zhang, Harshad S. Mahadeshwar, Jiabin Tang, Xiaojia Ren, Sahil Seth, Psalm Haseley, Dong Zeng, Lixing Yang, Andrew W. Xu, Xingzhi Song, Angeliki Pantazi, Christopher A. Bristow, Angela Hadjipanayis, Jonathan Seidman, Lynda Chin

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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.

LanguageEnglish (US)
Pages576-582
Number of pages7
JournalNature
Volume517
Issue number7536
DOIs
StatePublished - Jan 29 2015

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Mutation
Neoplasms
TNF Receptor-Associated Factor 3
cdc Genes
Atlases
Oncogenes
Chromatin
Mouth
Oxidative Stress
Smoking
Genome
Carcinoma, squamous cell of head and neck
Genes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Comprehensive genomic characterization of head and neck squamous cell carcinomas. / The Cancer Genome Atlas Network.

In: Nature, Vol. 517, No. 7536, 29.01.2015, p. 576-582.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Network 2015, 'Comprehensive genomic characterization of head and neck squamous cell carcinomas' Nature, vol. 517, no. 7536, pp. 576-582. DOI: 10.1038/nature14129
The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015 Jan 29;517(7536):576-582. Available from, DOI: 10.1038/nature14129
The Cancer Genome Atlas Network. / Comprehensive genomic characterization of head and neck squamous cell carcinomas. In: Nature. 2015 ; Vol. 517, No. 7536. pp. 576-582
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