The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

• Published in: Science (American Association for the Advancement of Science) Vol. 333; no. 6046; pp. 1157 - 1160
• 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: Washington, DC American Association for the Advancement of Science 26.08.2011; The American Association for the Advancement of Science
• Subjects: Algorithms; Apoptosis; Biological and medical sciences; Cancer; Carcinogenesis; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - virology; Carcinoma, Squamous Cell; Cell Differentiation; Coding; Environmental Influences; Epidemiology; Etiology; Exons; Genes; Genetic mutation; Genetics; Genomes; Head; Head & neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - virology; Human papillomavirus; Humans; Independent Study; Individualized Instruction; Medical sciences; Mutation; Neck; Neoplasms, Squamous Cell - genetics; Neoplasms, Squamous Cell - metabolism; Neoplasms, Squamous Cell - virology; Nicotiana; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Papillomaviridae - isolation & purification; Papillomavirus Infections - virology; Point Mutation; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; Risk factors; Sequence Analysis, DNA; Sequence Deletion; Sequencing; Signal Transduction; Smoking; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Tobacco; Tumors; Human; TP63 gene; Tobacco smoking; Papovaviridae; Malignant tumor; Carcinogenesis; Infection; Papillomavirus; Virus; Human papillomavirus; Cancerology; Viral disease; Exome sequencing; Genetics; ENT disease; Head and neck cancer; Head and neck squamous cell carcinoma; Mutation; Interferon regulatory factor; Cancer; Tumor suppressor gene
• ISSN: 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.