The mutational landscape of head and neck squamous cell carcinoma

• Published in: Science (American Association for the Advancement of Science) Vol. 333; no. 6046; p. 1157
• Main Authors: Stransky, Nicolas, Egloff, Ann Marie, Tward, Aaron D, Kostic, Aleksandar D, Cibulskis, Kristian, Sivachenko, Andrey, Kryukov, Gregory V, Lawrence, Michael S, Sougnez, Carrie, McKenna, Aaron, Shefler, Erica, Ramos, Alex H, Stojanov, Petar, Carter, Scott L, Voet, Douglas, Cortés, Maria L, Auclair, Daniel, Berger, Michael F, Saksena, Gordon, Guiducci, Candace, Onofrio, Robert C, Parkin, Melissa, Romkes, Marjorie, Weissfeld, Joel L, Seethala, Raja R, Wang, Lin, Rangel-Escareño, Claudia, Fernandez-Lopez, Juan Carlos, Hidalgo-Miranda, Alfredo, Melendez-Zajgla, Jorge, Winckler, Wendy, Ardlie, Kristin, Gabriel, Stacey B, Meyerson, Matthew, Lander, Eric S, Getz, Gad, Golub, Todd R, Garraway, Levi A, Grandis, Jennifer R
• Format: Journal Article
• Language: English
• Published: United States 26.08.2011
• Subjects: Algorithms; Apoptosis; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - virology; Carcinoma, Squamous Cell; Cell Differentiation; Exons; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - virology; Humans; Mutation; Neoplasms, Squamous Cell - genetics; Neoplasms, Squamous Cell - metabolism; Neoplasms, Squamous Cell - virology; Papillomaviridae - isolation & purification; Papillomavirus Infections - virology; Point Mutation; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; Sequence Analysis, DNA; Sequence Deletion; Signal Transduction; Smoking; Squamous Cell Carcinoma of Head and Neck; Tobacco Products
• ISSN: 1095-9203; 0036-8075; 1095-9203
• DOI: 10.1126/science.1208130

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.