title: The mutational landscape of head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stransky
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Egloff
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Tward
authors.forename: Aleksandar D
authors.initials: AD
authors.lastname: Kostic
authors.forename: Kristian
authors.initials: K
authors.lastname: Cibulskis
authors.forename: Andrey
authors.initials: A
authors.lastname: Sivachenko
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Kryukov
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.forename: Carrie
authors.initials: C
authors.lastname: Sougnez
authors.forename: Aaron
authors.initials: A
authors.lastname: McKenna
authors.forename: Erica
authors.initials: E
authors.lastname: Shefler
authors.forename: Alex H
authors.initials: AH
authors.lastname: Ramos
authors.forename: Petar
authors.initials: P
authors.lastname: Stojanov
authors.forename: Scott L
authors.initials: SL
authors.lastname: Carter
authors.forename: Douglas
authors.initials: D
authors.lastname: Voet
authors.forename: Maria L
authors.initials: ML
authors.lastname: Cortés
authors.forename: Daniel
authors.initials: D
authors.lastname: Auclair
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.forename: Gordon
authors.initials: G
authors.lastname: Saksena
authors.forename: Candace
authors.initials: C
authors.lastname: Guiducci
authors.forename: Robert C
authors.initials: RC
authors.lastname: Onofrio
authors.forename: Melissa
authors.initials: M
authors.lastname: Parkin
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Claudia
authors.initials: C
authors.lastname: Rangel-Escareño
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fernandez-Lopez
authors.forename: Alfredo
authors.initials: A
authors.lastname: Hidalgo-Miranda
authors.forename: Jorge
authors.initials: J
authors.lastname: Melendez-Zajgla
authors.forename: Wendy
authors.initials: W
authors.lastname: Winckler
authors.forename: Kristin
authors.initials: K
authors.lastname: Ardlie
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
mesh_terms: D000465:Algorithms; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell; D002454:Cell Differentiation; D005091:Exons; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D009154:Mutation; D018307:Neoplasms, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000821:virology; D017354:Point Mutation; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D015398:Signal Transduction; D012907:Smoking; D000077195:Squamous Cell Carcinoma of Head and Neck; D062789:Tobacco Products
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1