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

Nishant Agrawal, Mitchell J. Frederick, Curtis R. Pickering, Chetan Bettegowda, Kyle Chang, Ryan Li, Carole Fakhry, Tong Xin Xie, Jiexin Zhang, Jing Wang, Nianxiang Zhang, Adel K. El-Naggar, Samar A. Jasser, John N. Weinstein, Lisa Treviño, Jennifer A. Drummond, Donna M. Muzny, Yuanqing Wu, Laura D. Wood, Ralph H. Hruban & 11 others William H. Westra, Wayne M. Koch, Joseph A. Califano, Richard A. Gibbs, David Sidransky, Bert Vogelstein, Victor E. Velculescu, Nickolas Papadopoulos, David A. Wheeler, Kenneth W. Kinzler, Jeffrey N. Myers

Research output: Contribution to journalArticle

1017 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1154-1157
Number of pages4
JournalScience
Volume333
Issue number6046
DOIs
StatePublished - Aug 26 2011
Externally publishedYes

Fingerprint

Exome
Mutation
Neoplasms
Tobacco Use
Carcinoma, squamous cell of head and neck
Gene Dosage
Tumor Suppressor Genes
Oncogenes
Genes

ASJC Scopus subject areas

  • General

Cite this

Agrawal, N., Frederick, M. J., Pickering, C. R., Bettegowda, C., Chang, K., Li, R., ... Myers, J. N. (2011). Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science, 333(6046), 1154-1157. https://doi.org/10.1126/science.1206923

Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. / Agrawal, Nishant; Frederick, Mitchell J.; Pickering, Curtis R.; Bettegowda, Chetan; Chang, Kyle; Li, Ryan; Fakhry, Carole; Xie, Tong Xin; Zhang, Jiexin; Wang, Jing; Zhang, Nianxiang; El-Naggar, Adel K.; Jasser, Samar A.; Weinstein, John N.; Treviño, 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.

In: Science, Vol. 333, No. 6046, 26.08.2011, p. 1154-1157.

Research output: Contribution to journalArticle

Agrawal, N, Frederick, MJ, Pickering, CR, Bettegowda, C, Chang, K, Li, R, Fakhry, C, Xie, TX, 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 2011, 'Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1', Science, vol. 333, no. 6046, pp. 1154-1157. https://doi.org/10.1126/science.1206923
Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li R et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011 Aug 26;333(6046):1154-1157. https://doi.org/10.1126/science.1206923
Agrawal, Nishant ; Frederick, Mitchell J. ; Pickering, Curtis R. ; Bettegowda, Chetan ; Chang, Kyle ; Li, Ryan ; Fakhry, Carole ; Xie, Tong Xin ; Zhang, Jiexin ; Wang, Jing ; Zhang, Nianxiang ; El-Naggar, Adel K. ; Jasser, Samar A. ; Weinstein, John N. ; Treviño, 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. / Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. In: Science. 2011 ; Vol. 333, No. 6046. pp. 1154-1157.
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AU - Li, Ryan

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