Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in <i>NOTCH1</i>

Nishant Agrawal(Howard Hughes Medical Institute), Mitchell J. Frederick(The University of Texas MD Anderson Cancer Center), Curtis R. Pickering(The University of Texas MD Anderson Cancer Center), Chetan Bettegowda(Howard Hughes Medical Institute), Kyle Chang(Baylor College of Medicine), Ryan J. Li(Johns Hopkins University), Carole Fakhry(Johns Hopkins University), Tong-Xin Xie(The University of Texas MD Anderson Cancer Center), Jiexin Zhang(The University of Texas MD Anderson Cancer Center), Jing Wang(The University of Texas MD Anderson Cancer Center), Nianxiang Zhang(The University of Texas MD Anderson Cancer Center), Adel K. El‐Naggar(The University of Texas MD Anderson Cancer Center), Samar A. Jasser(The University of Texas MD Anderson Cancer Center), John N. Weinstein(The University of Texas MD Anderson Cancer Center), Lisa R. Treviño(Baylor College of Medicine), Jennifer Drummond(Baylor College of Medicine), Donna M. Muzny(Baylor College of Medicine), Yuanqing Wu(Baylor College of Medicine), Laura D. Wood(Johns Hopkins University), Ralph H. Hruban(Johns Hopkins University), William H. Westra(Johns Hopkins University), Wayne M. Koch(Johns Hopkins University), Joseph A. Califano(Greater Baltimore Medical Center), Richard A. Gibbs(Greater Baltimore Medical Center), David Sidransky(Johns Hopkins University), Bert Vogelstein(Howard Hughes Medical Institute), Victor E. Velculescu(Howard Hughes Medical Institute), Nickolas Papadopoulos(Howard Hughes Medical Institute), David A. Wheeler(Baylor College of Medicine), Kenneth W. Kinzler(Howard Hughes Medical Institute), Jeffrey N. Myers(The University of Texas MD Anderson Cancer Center)
Science
July 28, 2011
10.1126/science.1206923
Cited by 1,691

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.

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