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The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

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

in Algorithms / Apoptosis / Biological and medical sciences / Cancer / Carcinogenesis / Carcinoma - genetics / Carcinoma - metabolism / Carcinoma - virology / Carcinoma, Squamous Cell / Cell Differentiation / Coding / DNA / Environmental factors / 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 / Otorhinolaryngology (head neck, general aspects and miscellaneous) / Otorhinolaryngology. Stomatology / Papillomaviridae / 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 / Tobacco Products / Tumors

2011

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2011

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2011

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Journal Article

The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

Kryukov, Gregory V.,

Sougnez, Carrie,

Weissfeld, Joel L.,

Rangel-Escareño, Claudia,

Tward, Aaron D.,

Golub, Todd R.,

Shefler, Erica,

Winckler, Wendy,

Fernandez-Lopez, Juan Carlos,

McKenna, Aaron,

Ramos, Alex H.,

Parkin, Melissa,

Carter, Scott L.,

Romkes, Marjorie,

Egloff, Ann Marie,

Auclair, Daniel,

Sivachenko, Andrey,

Kostic, Aleksandar D.,

Guiducci, Candace,

Lawrence, Michael S.,

Saksena, Gordon,

Cortés, Maria L.,

Lander, Eric S.,

Seethala, Raja R.,

Onofrio, Robert C.,

Cibulskis, Kristian,

Voet, Douglas,

Hidalgo-Miranda, Alfredo,

Meyerson, Matthew,

Stransky, Nicolas,

Grandis, Jennifer R.,

Melendez-Zajgla, Jorge,

Garraway, Levi A.,

Gabriel, Stacey B.,

Wang, Lin,

Berger, Michael F.,

Ardlie, Kristin,

Getz, Gad,

Stojanov, Petar

2011

Overview

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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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

Algorithms

/ Apoptosis

/ Biological and medical sciences

/ Cancer

/ Carcinogenesis

/ Carcinoma - genetics

/ Carcinoma - metabolism