Allele-Specific Tumor Spectrum in Pten Knockin Mice
Document Type
Article
Publication Date
3-16-2010
Description
Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan-Riley- Ruvalcaba (BRR) 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 patients with Cowden syndrome and show that the nonsense PtenΔ4-5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectrawith varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for PtenΔ4-5, hypomorphic function for PtenC124R, and gain of function for Pten G129E. These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specificmutations in PTEN that alter protein function through distinct mechanisms.
Citation Information
Wang, Hui; Karikomi, Matt; Naidu, Shan; Rajmohan, Ravi; Caserta, Enrico; Chen, Hui Zi; Rawahneh, Maysoon; Moffitt, Julie; Stephens, Julie A.; Fernandez, Soledad A.; Weinstein, Michael; Wang, Danxin; Sadee, Wolfgang; La Perle, Krista; Stromberg, Paul; Rosol, Thomas J.; Eng, Charis; Ostrowsk, Michael C.; and Leone, Gustavo. 2010. Allele-Specific Tumor Spectrum in Pten Knockin Mice. Proceedings of the National Academy of Sciences of the United States of America. Vol.107(11). 5142-5147. https://doi.org/10.1073/pnas.0912524107 PMID: 20194734 ISSN: 0027-8424