Evolutionary action score of TP53 coding variants is predictive of platinum response in head and neck cancer patients

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 KimmeMitchell J. Frederick, Olivier Lichtarge, Jeffrey N. Myers

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1205-1215
Number of pages11
JournalCancer Research
Volume75
Issue number7
DOIs
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Osman, A. A., Neskey, D. M., Katsonis, P., Patel, A. A., Ward, A. M., Hsu, T. K., Hicks, S. C., McDonald, T. O., Ow, T. J., Alves, M. O., Pickering, C. R., Skinner, H. D., Zhao, M., Sturgis, E. M., Kies, M. S., El-Naggar, A., Perrone, F., Licitra, L., Bossi, P., ... Myers, J. N. (2015). Evolutionary action score of TP53 coding variants is predictive of platinum response in head and neck cancer patients. Cancer Research, 75(7), 1205-1215. https://doi.org/10.1158/0008-5472.CAN-14-2729