Title | Comprehensive genomic characterization of head and neck squamous cell carcinomas. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Corporate Authors | Cancer Genome Atlas Network |
Journal | Nature |
Volume | 517 |
Issue | 7536 |
Pagination | 576-82 |
Date Published | 2015 Jan 29 |
ISSN | 1476-4687 |
Keywords | 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, Squamous Cell Carcinoma of Head and Neck, 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. |
DOI | 10.1038/nature14129 |
Alternate Journal | Nature |
PubMed ID | 25631445 |
PubMed Central ID | PMC4311405 |
Grant List | UL1 TR000433 / TR / NCATS NIH HHS / United States U24 CA143882 / CA / NCI NIH HHS / United States K08 DE024774 / DE / NIDCR NIH HHS / United States U24 CA143843 / CA / NCI NIH HHS / United States U54 HG003079 / HG / NHGRI NIH HHS / United States ZIA-DC-000073 / DC / NIDCD NIH HHS / United States U24 CA143883 / CA / NCI NIH HHS / United States R01 CA095419 / CA / NCI NIH HHS / United States U24 CA143867 / CA / NCI NIH HHS / United States R01 DE023685 / DE / NIDCR NIH HHS / United States UL1 TR000005 / TR / NCATS NIH HHS / United States P30 CA016672 / CA / NCI NIH HHS / United States ZIA DC000016 / ImNIH / Intramural NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States U24 CA143835 / CA / NCI NIH HHS / United States P30 CA047904 / CA / NCI NIH HHS / United States U24 CA143866 / CA / NCI NIH HHS / United States P50CA097190 / CA / NCI NIH HHS / United States U24 CA143845 / CA / NCI NIH HHS / United States U24 CA143799 / CA / NCI NIH HHS / United States R01 CA 095419 / CA / NCI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States U24 CA144025 / CA / NCI NIH HHS / United States U24 CA180951 / CA / NCI NIH HHS / United States U24 CA143840 / CA / NCI NIH HHS / United States U24 CA143858 / CA / NCI NIH HHS / United States ZIA-DC-000074 / DC / NIDCD NIH HHS / United States P50CA16672 / CA / NCI NIH HHS / United States P30 CA177558 / CA / NCI NIH HHS / United States R01 HG006272 / HG / NHGRI NIH HHS / United States P50 CA097190 / CA / NCI NIH HHS / United States U24 CA143848 / CA / NCI NIH HHS / United States |
Comprehensive genomic characterization of head and neck squamous cell carcinomas.
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