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 J. 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; 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

doi:10.1126/science.1206923

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 J. 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. HrubanWilliam 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

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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 language	English (US)
Pages (from-to)	1154-1157
Number of pages	4
Journal	Science
Volume	333
Issue number	6046
DOIs	https://doi.org/10.1126/science.1206923
State	Published - Aug 26 2011

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Agrawal, N., Frederick, M. J., Pickering, C. R., Bettegowda, C., Chang, K., Li, R. J., Fakhry, C., Xie, T. X., Zhang, J., Wang, J., Zhang, N., El-Naggar, A. K., Jasser, S. A., Weinstein, J. N., Treviño, L., Drummond, J. A., Muzny, D. M., Wu, Y., Wood, L. D., ... 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

Agrawal, N, Frederick, MJ, Pickering, CR, Bettegowda, C, Chang, K, Li, RJ, 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

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title = "Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1",

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.",

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

year = "2011",

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AU - Agrawal, Nishant

AU - Frederick, Mitchell J.

AU - Pickering, Curtis R.

AU - Bettegowda, Chetan

AU - Chang, Kyle

AU - Li, Ryan J.

AU - Fakhry, Carole

AU - Xie, Tong Xin

AU - Zhang, Jiexin

AU - Wang, Jing

AU - Zhang, Nianxiang

AU - El-Naggar, Adel K.

AU - Jasser, Samar A.

AU - Weinstein, John N.

AU - Treviño, Lisa

AU - Drummond, Jennifer A.

AU - Muzny, Donna M.

AU - Wu, Yuanqing

AU - Wood, Laura D.

AU - Hruban, Ralph H.

AU - Westra, William H.

AU - Koch, Wayne M.

AU - Califano, Joseph A.

AU - Gibbs, Richard A.

AU - Sidransky, David

AU - Vogelstein, Bert

AU - Velculescu, Victor E.

AU - Papadopoulos, Nickolas

AU - Wheeler, David A.

AU - Kinzler, Kenneth W.

AU - Myers, Jeffrey N.

PY - 2011/8/26

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N2 - 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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Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1

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