Mutations of the human PTEN gene

Hum Mutat. 2000;16(2):109-22. doi: 10.1002/1098-1004(200008)16:2<109::AID-HUMU3>3.0.CO;2-0.


PTEN (phosphatase and tensin homolog deleted on chromosome ten), a recently discovered tumor suppressor gene, appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell proliferation and cell survival by dephosphorylating the phosphatidylinositol 3,4,5-triphosphate. To date, 110 germline PTEN mutations have been reported in patients affected with two tumor predisposing syndromes, each having overlapping clinical features: Cowden disease and Bannayan-Riley-Ruvalcaba syndrome. These 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 phosphatase 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 or metastasis, have been reviewed. Somatic PTEN mutations are more particularly involved in two types of human cancers: endometrial carcinomas and glioblastomas. In most cases, these somatic mutations result in protein inactivation and, as with germline mutations, recurrent somatic mutations are found in CpG dinucleotides. A mutagenesis by insertion-deletion in repetitive elements is however specifically observed in endometrial carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Frameshift Mutation / genetics
  • Genes, Tumor Suppressor / genetics*
  • Germ-Line Mutation / genetics*
  • Hamartoma Syndrome, Multiple / genetics*
  • Humans
  • Mutation, Missense
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / deficiency
  • Phosphoric Monoester Hydrolases / genetics*
  • Point Mutation / genetics
  • Tumor Suppressor Proteins*


  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human