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Cancer Res. 2015 Apr 1;75(7):1205-15. doi: 10.1158/0008-5472.CAN-14-2729. Epub 2015 Feb 17.

Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients.

Author information

1
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Otolaryngology Head and Neck Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
3
Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.
4
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
5
Department of Statistics, Rice University, Houston, Texas.
6
Department of Otolaryngology Head and Neck Surgery, Albert Einstein School of Medicine, Bronx, New York.
7
Department of Internal Medicine, Tufts Medical Center, Boston, Massachusetts.
8
Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
9
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
10
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
11
Department of Pathology, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy.
12
Head and Neck Medical Oncology Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy.
13
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. jmyers@mdanderson.org.

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.

PMID:
25691460
PMCID:
PMC4615655
DOI:
10.1158/0008-5472.CAN-14-2729
[Indexed for MEDLINE]
Free PMC Article

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