Osman, Abdullah A.Neskey, David M.Katsonis, PanagiotisPatel, Ameeta A.Ward, Alexandra M.Hsu, Teng-KueiHicks, Stephanie C.McDonald, Thomas O.Ow, Thomas J.Alves, Marcus OrtegaPickering, Curtis R.Skinner, Heath D.Zhao, MeiSturgis, Eric M.Kies, Merrill S.El-Naggar, AdelPerrone, FedericaLicitra, LisaBossi, PaoloKimmel, MarekFrederick, Mitchell J.Lichtarge, OlivierMyers, Jeffrey N.2017-05-152017-05-152015Osman, Abdullah A., Neskey, David M., Katsonis, Panagiotis, et al.. "Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients." <i>Cancer Research,</i> 75, no. 7 (2015) AACR: 1205-1215. http://dx.doi.org/10.1158/0008-5472.CAN-14-2729.https://hdl.handle.net/1911/94253TP53 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.engThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by AACR.Journal articlehttp://dx.doi.org/10.1158/0008-5472.CAN-14-2729