Colorectal carcinomas and PTEN/MMAC1 gene mutations

Purpose: PTEN/MMAC1/TEP1 is a tumor suppressor gene encoding a dual-specificity protein phosphatase with homology to the cytoskeleton proteins, chicken tensin and bovine auxilin. PTEN mutations have been described in several types of human cancer. Recently, mutations at an (A)6 repeat of PTEN exons 7 and 8 in colorectal cancer (CRC) patients with microsatellite instability have been detected. Moreover, an involvement of the transforming growth factor (TGF)-β pathway in hereditary colorectal syndromes has been proposed. Experimental Design: In this study, we analyzed the frequency of PTEN gene mutations in 36 CRC patients and 5 colon cancer cell lines. Furthermore, in 16 of 36 patients, microsatellite instability and TGF-β receptor II analysis was possible. The study was performed by PCR and automated sequencing of the entire coding region of the PTEN gene. Results: About 17% of colon cancer patients and one of five (HSR 320) colon cancer cell lines had mutations. Mutations were detected only among patients with locally advanced or metastatic CRC. PTEN mutations were detected in three of five (60%) patients showing both microsatellite instability and TGF-β receptor II mutations. These patients presented with advanced or metastatic CRC. Conclusions: Overall, these results show that PTEN alteration together with TGF-β pathway inactivation could contribute to tumorigenesis and metastatic spread of sporadic and microsatellite unstable CRC