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 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.

1. Chen J et al. Low expression of phosphatase and tensin homolog in clear-cell renal cell carcinoma contributes to chemoresistance through activating the Akt/HDM2 signaling pathway. Mol Med Rep 12:2622-8 (2015).
2. Zeng C et al. SPOP suppresses tumorigenesis by regulating hedgehog/Gli2 signaling pathway in gastric cancer. J Exp Clin Cancer Res 33:75 (2014).