title: Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.
abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. nagrawal@jhmi.edu
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Frederick
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Pickering
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.forename: Kyle
authors.initials: K
authors.lastname: Chang
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Li
authors.forename: Carole
authors.initials: C
authors.lastname: Fakhry
authors.forename: Tong-Xin
authors.initials: TX
authors.lastname: Xie
authors.forename: Jiexin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Nianxiang
authors.initials: N
authors.lastname: Zhang
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Samar A
authors.initials: SA
authors.lastname: Jasser
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.forename: Lisa
authors.initials: L
authors.lastname: Treviño
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Drummond
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Wu
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
mesh_terms: D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D002294:Carcinoma, Squamous Cell; D018797:Cell Cycle Proteins / Q000235:genetics*; D018389:Codon, Nonsense; D005091:Exons; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D054643:INDEL Mutation; D009154:Mutation; D020125:Mutation, Missense; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000821:virology; D051881:Receptor, Notch1 / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012907:Smoking; D000077195:Squamous Cell Carcinoma of Head and Neck; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D044767:Ubiquitin-Protein Ligases