Comprehensive genomic characterization of head and neck squamous cell carcinomas

The Cancer Genome Atlas Network

Research output: Contribution to journalArticle

1152 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)576-582
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

All Science Journal Classification (ASJC) codes

  • General

Cite this

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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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

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AU - The Cancer Genome Atlas Network

AU - Lawrence, Michael S.

AU - Sougnez, Carrie

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AU - Robertson, A. Gordon

AU - Schein, Jacqueline E.

AU - Sipahimalani, Payal

AU - Tam, Angela

AU - Thiessen, Nina

AU - Wong, Tina

AU - Protopopov, Alexei

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AU - Lee, Semin

AU - Parfenov, Michael

AU - Zhang, Jianhua

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AU - Tang, Jiabin

AU - Ren, Xiaojia

AU - Seth, Sahil

AU - Haseley, Psalm

AU - Zeng, Dong

AU - Yang, Lixing

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