Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer.

ABSTRACT: TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutati

SUBMITTER: Neskey DM 

PROVIDER: S-EPMC4383697 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature