Mutations of the human PTEN gene

PTEN (phosphatase and tensin homolog deleted on chromosome ten), a recently discovered tumor suppressor gene, appears to negatively control the phosph oinositide 3-kinase signaling path way for regulation of cell proliferation and cell survival by dephosphorylating the phosphatidylinositol 3,4,5-trip hosphate. To date, 110 germline PTEN mutations have been reported in patien ts affected with two tumor predisposing syndromes, each having overlapping clinical features: Cowden disease and Bannayan-Riley-Ruvalcaba syndrome. Th ese germline mutations are scattered along the length of the gene, with the exception of exon 9 (no mutation reported) and exon 1 (only two mutations reported). A mutational hot spot is found in exon 5, which encodes the phos phatase catalytic core motif, and recurrent mutations are also found at CpG dinucleotides suggesting deamination-induced mutations. PTEN has also been found to be defective in a large number of sporadic human tumors. In this article, 332 somatic point mutations of PTEN, occurring in primary tumors o r metastasis, have been reviewed. Somatic PTEN mutations are more particula rly involved in two types of human cancers: endometrial carcinomas and glio blastomas, In most cases, these somatic mutations result in protein inactiv ation and, as with germline mutations, recurrent somatic mutations are foun d in CpG dinucleotides. A mutagenesis by insertion-deletion in repetitive e lements is however specifically observed in endometrial carcinomas. Hum Mut at 16:109-122, 2000. (C) 2000 Wiley-Liss, Inc.