Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.

TitleExome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.
Publication TypeJournal Article
Year of Publication2011
AuthorsAgrawal, N, Frederick, MJ, Pickering, CR, Bettegowda, C, Chang, K, Li, RJ, Fakhry, C, Xie, T-X, Zhang, J, Wang, J, Zhang, N, El-Naggar, AK, Jasser, SA, Weinstein, JN, Treviño, L, Drummond, JA, Muzny, DM, Wu, Y, Wood, LD, Hruban, RH, Westra, WH, Koch, WM, Califano, JA, Gibbs, RA, Sidransky, D, Vogelstein, B, Velculescu, VE, Papadopoulos, N, Wheeler, DA, Kinzler, KW, Myers, JN
JournalScience
Volume333
Issue6046
Pagination1154-7
Date Published2011 Aug 26
ISSN1095-9203
KeywordsCarcinoma, Carcinoma, Squamous Cell, Cell Cycle Proteins, Codon, Nonsense, Exons, F-Box Proteins, F-Box-WD Repeat-Containing Protein 7, Gene Dosage, Genes, p53, Genes, Tumor Suppressor, Head and Neck Neoplasms, Humans, INDEL Mutation, Mutation, Mutation, Missense, Neoplasms, Squamous Cell, Oligonucleotide Array Sequence Analysis, Oncogenes, Papillomaviridae, Papillomavirus Infections, Receptor, Notch1, Sequence Analysis, DNA, Smoking, Squamous Cell Carcinoma of Head and Neck, Tobacco, Ubiquitin-Protein Ligases
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.

DOI10.1126/science.1206923
Alternate JournalScience
PubMed ID21798897
PubMed Central IDPMC3162986
Grant ListCA57345 / CA / NCI NIH HHS / United States
R37 CA043460 / CA / NCI NIH HHS / United States
P50 CA097007 / CA / NCI NIH HHS / United States
CA121113 / CA / NCI NIH HHS / United States
CN43302 / CN / NCI NIH HHS / United States
R37 CA043460-16 / CA / NCI NIH HHS / United States
RC2DE020958 / DE / NIDCR NIH HHS / United States
CA16672 / CA / NCI NIH HHS / United States
N01CN43302 / CA / NCI NIH HHS / United States
R01 CA121113-01 / CA / NCI NIH HHS / United States
RC2 DE020957-01 / DE / NIDCR NIH HHS / United States
R37 DE012588-14 / DE / NIDCR NIH HHS / United States
R01 CA121113 / CA / NCI NIH HHS / United States
RC2 DE020958 / DE / NIDCR NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
CA43460 / CA / NCI NIH HHS / United States
P50 CA097007-05 / CA / NCI NIH HHS / United States
P50 DE019032-07 / DE / NIDCR NIH HHS / United States
P50 DE019032-10 / DE / NIDCR NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
P50 DE019032 / DE / NIDCR NIH HHS / United States
RC2DE020957 / DE / NIDCR NIH HHS / United States
P50DE019032 / DE / NIDCR NIH HHS / United States
R37 CA057345 / CA / NCI NIH HHS / United States
T32 CA009574 / CA / NCI NIH HHS / United States
RC2 DE020958-02 / DE / NIDCR NIH HHS / United States
R37 DE012588 / DE / NIDCR NIH HHS / United States
RC2 DE020957-02 / DE / NIDCR NIH HHS / United States
R37 CA057345-20 / CA / NCI NIH HHS / United States
RC2 DE020957 / DE / NIDCR NIH HHS / United States
5P50CA09700708 / CA / NCI NIH HHS / United States
N01 CN043302 / CN / NCI NIH HHS / United States