Abstract 3260: Allele-specific tumor spectrum in Pten knockin mice

Abstract Germline mutations in the PTEN tumor suppressor cause Cowden and Bannayan-Riley-Ruvalcaba syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas and variable cancer risk. Here we modeled three sentinel mutant alleles of PTEN identified in Cowden patients and show that the nonsense PtenΔ4–5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectra with varying severity and age-of-onset. Allele-specific differences may be accounted by loss-of-function for Pten Δ4-5, hypomorphic function for PtenC124R and gain-of-function for PtenG129E. These data demonstrate that the variable tumor phenotypes observed in Cowden and Bannayan-Riley-Ruvalcaba syndrome patients can be attributed to specific mutations in PTEN that alter protein function through distinct mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3260.