The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

作者：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; Cortes 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 Escareno Claudia; Carlos Fernandez Lopez Juan

来源：Science, 2011, 333(6046): 1157-1160.

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.

• 出版日期2011-8-26