Publication Date:
2011-07-30
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162986/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162986/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agrawal, Nishant -- Frederick, Mitchell J -- Pickering, Curtis R -- Bettegowda, Chetan -- Chang, Kyle -- Li, Ryan J -- Fakhry, Carole -- Xie, Tong-Xin -- Zhang, Jiexin -- Wang, Jing -- Zhang, Nianxiang -- El-Naggar, Adel K -- Jasser, Samar A -- Weinstein, John N -- Trevino, Lisa -- Drummond, Jennifer A -- Muzny, Donna M -- Wu, Yuanqing -- Wood, Laura D -- Hruban, Ralph H -- Westra, William H -- Koch, Wayne M -- Califano, Joseph A -- Gibbs, Richard A -- Sidransky, David -- Vogelstein, Bert -- Velculescu, Victor E -- Papadopoulos, Nickolas -- Wheeler, David A -- Kinzler, Kenneth W -- Myers, Jeffrey N -- 5P50CA09700708/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA16672/CA/NCI NIH HHS/ -- CA43460/CA/NCI NIH HHS/ -- CA57345/CA/NCI NIH HHS/ -- CN43302/CN/NCI NIH HHS/ -- N01 CN043302/CN/NCI NIH HHS/ -- P50 CA097007/CA/NCI NIH HHS/ -- P50 CA097007-05/CA/NCI NIH HHS/ -- P50 DE019032/DE/NIDCR NIH HHS/ -- P50 DE019032-07/DE/NIDCR NIH HHS/ -- P50 DE019032-10/DE/NIDCR NIH HHS/ -- P50DE019032/DE/NIDCR NIH HHS/ -- R01 CA121113/CA/NCI NIH HHS/ -- R01 CA121113-01/CA/NCI NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37 CA043460-16/CA/NCI NIH HHS/ -- R37 CA057345/CA/NCI NIH HHS/ -- R37 CA057345-20/CA/NCI NIH HHS/ -- R37 DE012588/DE/NIDCR NIH HHS/ -- R37 DE012588-14/DE/NIDCR NIH HHS/ -- RC2 DE020957/DE/NIDCR NIH HHS/ -- RC2 DE020957-01/DE/NIDCR NIH HHS/ -- RC2 DE020957-02/DE/NIDCR NIH HHS/ -- RC2 DE020958/DE/NIDCR NIH HHS/ -- RC2 DE020958-02/DE/NIDCR NIH HHS/ -- RC2DE020957/DE/NIDCR NIH HHS/ -- RC2DE020958/DE/NIDCR NIH HHS/ -- T32 CA009574/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1154-7. doi: 10.1126/science.1206923. Epub 2011 Jul 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. nagrawal@jhmi.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21798897" target="_blank"〉PubMed〈/a〉
Keywords:
Carcinoma/drug therapy/*genetics/virology
;
Carcinoma, Squamous Cell
;
Cell Cycle Proteins/*genetics
;
Codon, Nonsense
;
Exons
;
F-Box Proteins/*genetics
;
Gene Dosage
;
*Genes, Tumor Suppressor
;
Genes, p53
;
Head and Neck Neoplasms/drug therapy/*genetics/virology
;
Humans
;
INDEL Mutation
;
*Mutation
;
Mutation, Missense
;
Neoplasms, Squamous Cell/drug therapy/*genetics/virology
;
Oligonucleotide Array Sequence Analysis
;
Oncogenes
;
Papillomaviridae/isolation & purification
;
Papillomavirus Infections/virology
;
Receptor, Notch1/chemistry/*genetics
;
Sequence Analysis, DNA
;
Smoking
;
Tobacco
;
Ubiquitin-Protein Ligases/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
