Comprehensive genomic characterization of head and neck squamous cell carcinomas.

TitleComprehensive genomic characterization of head and neck squamous cell carcinomas.
Publication TypeJournal Article
Year of Publication2015
Corporate Authors
JournalNature
Volume517
Issue7536
Pagination576-82
Date Published2015 Jan 29
ISSN1476-4687
KeywordsCarcinoma, 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
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.

DOI10.1038/nature14129
Alternate JournalNature
PubMed ID25631445
PubMed Central IDPMC4311405
Grant ListK08 DE024774 / DE / NIDCR NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
P50CA097190 / CA / NCI NIH HHS / United States
P50CA16672 / CA / NCI NIH HHS / United States
R01 CA 095419 / CA / NCI NIH HHS / United States
R01 DE023685 / DE / NIDCR NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA180951 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
UL1 TR000433 / TR / NCATS NIH HHS / United States
ZIA-DC-000016 / DC / NIDCD NIH HHS / United States
ZIA-DC-000073 / DC / NIDCD NIH HHS / United States
ZIA-DC-000074 / DC / NIDCD NIH HHS / United States
/ / Intramural NIH HHS / United States