Mutation of the PTEN gene in a human hepatic angiosarcoma.

The phosphatase and tensin homolog (mutated in multiple advanced cancers 1) gene, or 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). The PTEN protein inhibits angiogenesis, and somatic mutations of the PTEN gene are involved in canine hemangiosarcoma. We screened for mutations of the PTEN gene in two patients with human hepatic angiosarcoma to determine whether PTEN is involved in the pathogenesis of human hepatic angiosarcoma. In one patient, who suffered from breast cancer, pharyngeal cancer, and hepatic angiosarcoma, we found a single base substitution in exon 7 (640C>T) of the PTEN gene in both the hepatic angiosarcoma and normal tissues. This transition results in a germline nonsense mutation (Q214X). These findings indicate that analysis of PTEN gene mutations may be useful for characterization of the molecular event in hepatic angiosarcoma and cancer predisposition.