A novel mutation of the PTEN gene in a Japanese patient with Cowden syndrome and bilateral breast cancer.

Cowden syndrome (CS), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with a high risk of breast and thyroid cancers. The phosphatase and tensin homolog gene (PTEN) encodes a lipid phosphatase that contains a PTPase domain and a C2 domain and plays a role as a tumor suppressor that negatively regulates the cell-survival signaling pathway initiated by phosphatidylinositol 3-kinase (PI3K). PTEN inhibits angiogenesis, and germline mutations of the PTEN gene are associated with CS. We screened for mutations in the PTEN gene in two unrelated Japanese patients with CS. In one patient, who suffered from bilateral breast cancer, thyroid adenoma, and gastric malignant lymphoma, we found a single-base substitution in exon 2 (115G>C) of the PTEN gene. This transversion results in a germline missense mutation (A39P). To date, nine different mutations have been identified in exon 2 of the PTEN gene in patients with CS and variant CS; however, the A39P missense mutation has not been reported previously. We also detected a previously reported nonsense mutation, 697C>T, resulting in R233X.