The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

Nicolas Stransky(Broad Institute), Ann Marie Egloff(UPMC Hillman Cancer Center), Aaron D. Tward(Broad Institute), Aleksandar D. Kostic(Broad Institute), Kristian Cibulskis(Broad Institute), Andrey Sivachenko(Broad Institute), Gregory V. Kryukov(Broad Institute), Michael S. Lawrence(Broad Institute), Carrie Sougnez(Broad Institute), Aaron McKenna(Broad Institute), Erica Shefler(Broad Institute), Alex H. Ramos(Broad Institute), Petar Stojanov(Broad Institute), Scott L. Carter(Broad Institute), Douglas Voet(Broad Institute), Maria L. Cortés(Broad Institute), Daniel Auclair(Broad Institute), Michael F. Berger(Broad Institute), Gordon Saksena(Broad Institute), Candace Guiducci(Broad Institute), Robert C. Onofrio(Broad Institute), Melissa Parkin(Broad Institute), Marjorie Romkes(UPMC Hillman Cancer Center), Joel L. Weissfeld(UPMC Hillman Cancer Center), Raja R. Seethala(UPMC Hillman Cancer Center), Lin Wang(UPMC Hillman Cancer Center), Claudia Rangel‐Escareño(National Institute of Genomic Medicine), Juan Carlos Fernández-López(National Institute of Genomic Medicine), Alfredo Hidalgo‐Miranda(National Institute of Genomic Medicine), Jorge Meléndez-Zajgla(National Institute of Genomic Medicine), Wendy Winckler(Broad Institute), Kristin Ardlie(Broad Institute), Stacey Gabriel(Broad Institute), Matthew Meyerson(Broad Institute), Eric S. Lander(Broad Institute), Gad Getz(Broad Institute), Todd R. Golub(Broad Institute), Levi A. Garraway(Broad Institute), Jennifer R. Grandis(UPMC Hillman Cancer Center)
Science
July 28, 2011
10.1126/science.1208130
Cited by 2,539Open Access
Full Text

Abstract

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.

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