Presentation Abstract

Abstract Number: 3260
Presentation Title: Allele-specific tumor spectrum in Pten knockin mice
Presentation Time: Tuesday, Apr 20, 2010, 9:00 AM -12:00 PM
Location: Exhibit Hall A-C, Poster Section 13
Poster Section: 13
Poster Board Number: 7
Author Block: Hui Wang1, Matt Karikomi1, Shan Naidu1, Ravi Rajmohan1, Enrico Caserta1, Hui-Zi Chen1, Maysoon Rawahneh1, Julie Moffitt1, Julie A. Stephens1, Soledad A. Fernandez1, Michael Weinstein1, Krista La Perle1, Paul Stromberg1, Thomas J. Rosol1, Charis Eng2, Michael C. Ostrowski1, Gustavo Leone1. 1Ohio State Univ., Columbus, OH; 2Cleveland Clinic, Cleveland, OH
Abstract Body: 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 PtenΔ4-5, 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.