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Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015 Jan 29;517(7536):576-82

Date

01/30/2015

Pubmed ID

25631445

Pubmed Central ID

PMC4311405

DOI

10.1038/nature14129

Scopus ID

2-s2.0-84923197605   2459 Citations

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.

Author List

Cancer Genome Atlas Network

Author

Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Carcinoma, Squamous Cell
DNA Copy Number Variations
DNA, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Genome, Human
Genomics
Head and Neck Neoplasms
Humans
Male
Molecular Targeted Therapy
Mutation
Oncogenes
RNA, Neoplasm
Signal Transduction
Transcription Factors