Title | Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Agrawal, 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 |
Journal | Science |
Volume | 333 |
Issue | 6046 |
Pagination | 1154-7 |
Date Published | 2011 Aug 26 |
ISSN | 1095-9203 |
Keywords | Carcinoma, 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, Nicotiana, Oligonucleotide Array Sequence Analysis, Oncogenes, Papillomaviridae, Papillomavirus Infections, Receptor, Notch1, Sequence Analysis, DNA, Smoking, Squamous Cell Carcinoma of Head and Neck, 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. |
DOI | 10.1126/science.1206923 |
Alternate Journal | Science |
PubMed ID | 21798897 |
PubMed Central ID | PMC3162986 |
Grant List | N01CN43302 / CN / NCI NIH HHS / United States P50 CA097007 / CA / NCI NIH HHS / United States RC2DE020958 / DE / NIDCR NIH HHS / United States CA16672 / CA / NCI NIH HHS / United States R01 CA121113-01 / CA / NCI 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 T32 CA009574 / CA / NCI NIH HHS / United States RC2 DE020957-02 / DE / NIDCR NIH HHS / United States R37 CA057345-20 / CA / NCI NIH HHS / United States CA57345 / CA / NCI NIH HHS / United States R37 CA043460 / 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 / HHMI / Howard Hughes Medical Institute / 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 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 RC2 DE020958-02 / DE / NIDCR NIH HHS / United States R37 DE012588 / DE / NIDCR 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 |
Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.
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