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Science DOI:10.1126/science.1208130

The mutational landscape of head and neck squamous cell carcinoma.

Publication TypeJournal Article
Year of Publication2011
AuthorsStransky, N, Egloff, AMarie, Tward, AD, Kostic, AD, Cibulskis, K, Sivachenko, A, Kryukov, GV, Lawrence, MS, Sougnez, C, McKenna, A, Shefler, E, Ramos, AH, Stojanov, P, Carter, SL, Voet, D, Cortés, ML, Auclair, D, Berger, MF, Saksena, G, Guiducci, C, Onofrio, RC, Parkin, M, Romkes, M, Weissfeld, JL, Seethala, RR, Wang, L, Rangel-Escareño, C, Fernandez-Lopez, JCarlos, Hidalgo-Miranda, A, Melendez-Zajgla, J, Winckler, W, Ardlie, K, Gabriel, SB, Meyerson, M, Lander, ES, Getz, G, Golub, TR, Garraway, LA, Grandis, JR
Date Published2011 Aug 26
KeywordsAlgorithms, Apoptosis, Carcinoma, Carcinoma, Squamous Cell, Cell Differentiation, Exons, Head and Neck Neoplasms, Humans, Mutation, Neoplasms, Squamous Cell, Papillomaviridae, Papillomavirus Infections, Point Mutation, Receptor, Notch1, Sequence Analysis, DNA, Sequence Deletion, Signal Transduction, Smoking, Tobacco

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.


Alternate JournalScience
PubMed ID21798893
PubMed Central IDPMC3415217
Grant ListUL1 TR000005 / TR / NCATS NIH HHS / United States
R01 CA077308 / CA / NCI NIH HHS / United States
R01 CA098372 / CA / NCI NIH HHS / United States
P50 CA097190 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States