TY - JOUR
T1 - Evolutionary action score of TP53 coding variants is predictive of platinum response in head and neck cancer patients
AU - Osman, Abdullah A.
AU - Neskey, David M.
AU - Katsonis, Panagiotis
AU - Patel, Ameeta A.
AU - Ward, Alexandra M.
AU - Hsu, Teng Kuei
AU - Hicks, Stephanie C.
AU - McDonald, Thomas O.
AU - Ow, Thomas J.
AU - Alves, Marcus Ortega
AU - Pickering, Curtis R.
AU - Skinner, Heath D.
AU - Zhao, Mei
AU - Sturgis, Eric M.
AU - Kies, Merrill S.
AU - El-Naggar, Adel
AU - Perrone, Federica
AU - Licitra, Lisa
AU - Bossi, Paolo
AU - Kimme, Marek
AU - Frederick, Mitchell J.
AU - Lichtarge, Olivier
AU - Myers, Jeffrey N.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC), with mutations occurring in over two thirds of cases; however, the predictive response of these mutations to cisplatin-based therapy remains elusive. In the current study, we evaluate the ability of the Evolutionary Action score of TP53-coding variants (EAp53) to predict the impact of TP53 mutations on response to chemotherapy. The EAp53 approach clearly identifies a subset of high-risk TP53 mutations associated with decreased sensitivity to cisplatin both in vitro and in vivo in preclinical models of HNSCC. Furthermore, EAp53 can predict response to treatment and, more importantly, a survival benefit for a subset of head and neck cancer patients treated with platinum-based therapy. Prospective evaluation of this novel scoring system should enable more precise treatment selection for patients with HNSCC.
AB - TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC), with mutations occurring in over two thirds of cases; however, the predictive response of these mutations to cisplatin-based therapy remains elusive. In the current study, we evaluate the ability of the Evolutionary Action score of TP53-coding variants (EAp53) to predict the impact of TP53 mutations on response to chemotherapy. The EAp53 approach clearly identifies a subset of high-risk TP53 mutations associated with decreased sensitivity to cisplatin both in vitro and in vivo in preclinical models of HNSCC. Furthermore, EAp53 can predict response to treatment and, more importantly, a survival benefit for a subset of head and neck cancer patients treated with platinum-based therapy. Prospective evaluation of this novel scoring system should enable more precise treatment selection for patients with HNSCC.
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U2 - 10.1158/0008-5472.CAN-14-2729
DO - 10.1158/0008-5472.CAN-14-2729
M3 - Article
AN - SCOPUS:84930967437
VL - 75
SP - 1205
EP - 1215
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 7
ER -