As human tumors progress to advanced stages, one genetic alteration that occurs at high frequency is a loss of heterozygosity (LOH) at chromosome 10q23. Mapping of homozygous deletions on this chromosome led to the isolation of the PTEN gene, also designated MMAC1 (for mutated in multiple advanced cancers) and TEP1. This candidate tumor suppressor gene exhibits a high frequency of mutations in human glioblastomas and is also mutated in other cancers, including sporadic brain, breast, kidney and prostate cancers. PTEN has been associated with Cowden disease, an autosomal dominant cancer predisposition syndrome. The PTEN gene product is a putative protein tyrosine phosphatase that is localized to the cytoplasm, and it shares extensive homology with the cytoskeletal proteins Tensin and auxilin. Gene transfer studies have indicated that the phosphatase domain of PTEN is essential for growth suppression of glioma cells. PTEN contains five major phosphorylation sites and these are all located in the C-terminal 50 amino acid tail region (Ser 370, Ser 380, Thr 382, Thr 383 and Ser 385) and have been implicated in controlling PTEN activity