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The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

2011; American Association for the Advancement of Science; Volume: 333; Issue: 6046 Linguagem: Inglês

10.1126/science.1208130

1095-9203

Nicolas Stransky, Ann Marie Egloff, Aaron D. Tward, Aleksandar D. Kostic, Kristian Cibulskis, Andrey Sivachenko, Gregory V. Kryukov, Michael S. Lawrence, Carrie Sougnez, Aaron McKenna, Erica Shefler, Alex H. Ramos, Petar Stojanov, Scott L. Carter, Douglas Voet, Maria L. Cortés, Daniel Auclair, Michael F. Berger, Gordon Saksena, Candace Guiducci, Robert C. Onofrio, Melissa Parkin, Marjorie Romkes, Joel L. Weissfeld, Raja R. Seethala, Lin Wang, Claudia Rangel‐Escareño, Juan Carlos Fernández-López, Alfredo Hidalgo‐Miranda, Jorge Meléndez-Zajgla, Wendy Winckler, Kristin Ardlie, Stacey Gabriel, Matthew Meyerson, Eric S. Lander, Gad Getz, Todd R. Golub, Levi A. Garraway, Jennifer R. Grandis,

RNA Research and Splicing

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.