American Association for Cancer Research
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Methods and Materials from Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients

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journal contribution
posted on 2023-03-30, 23:45 authored by Abdullah A. Osman, David M. Neskey, Panagiotis Katsonis, Ameeta A. Patel, Alexandra M. Ward, Teng-Kuei Hsu, Stephanie C. Hicks, Thomas O. McDonald, Thomas J. Ow, Marcus Ortega Alves, Curtis R. Pickering, Heath D. Skinner, Mei Zhao, Eric M. Sturgis, Merrill S. Kies, Adel El-Naggar, Federica Perrone, Lisa Licitra, Paolo Bossi, Marek Kimmel, Mitchell J. Frederick, Olivier Lichtarge, Jeffrey N. Myers

Methods and Materials. Quantitative Reverse Transcription PCR (RT-qPCR) Analyses; mRNA Expression Arrays; Orthotopic Nude Mouse Model of Oral Cavity Cancer; Patient Cohort and TP53 Sequencing;Supplementary References;Footnotes.



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. Cancer Res; 75(7); 1205–15. ©2015 AACR.