The Mutational Landscape of Head and Neck Squamous Cell Carcinoma | Zendy

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

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The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

Author(s) -

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 RangelEscareño,

Juan Carlos Fernández-López,

Alfredo HidalgoMiranda,

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

Publication year - 2011

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1208130

Subject(s) - head and neck , basal cell , head and neck squamous cell carcinoma , carcinoma , biology , medicine , pathology , head and neck cancer , cancer , surgery

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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