title: Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients.
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.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Osman
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: David M
authors.initials: DM
authors.lastname: Neskey
authors.affiliation: Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Katsonis
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Ameeta A
authors.initials: AA
authors.lastname: Patel
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Ward
authors.affiliation: Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Teng-Kuei
authors.initials: TK
authors.lastname: Hsu
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Hicks
authors.affiliation: Department of Statistics, Rice University, Houston, Texas.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: McDonald
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Albert Einstein School of Medicine, Bronx, New York.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ow
authors.affiliation: Department of Internal Medicine, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Marcus Ortega
authors.initials: MO
authors.lastname: Alves
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Curtis R
authors.initials: CR
authors.lastname: Pickering
authors.affiliation: Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Heath D
authors.initials: HD
authors.lastname: Skinner
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Merrill S
authors.initials: MS
authors.lastname: Kies
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Adel
authors.initials: A
authors.lastname: El-Naggar
authors.affiliation: Department of Pathology, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Head and Neck Medical Oncology Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.affiliation: Head and Neck Medical Oncology Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bossi
authors.affiliation: Department of Statistics, Rice University, Houston, Texas.
authors.forename: Marek
authors.initials: M
authors.lastname: Kimmel
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Frederick
authors.affiliation: Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lichtarge
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. jmyers@mdanderson.org.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin