Frequent beta-catenin abnormalities in bone and soft-tissue tumors

We have screened mutations of the beta-catenin gene by using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method i n 62 malignant bone and soft-tissue tumors, including malignant fibrous his tiocytomas (MFHs), osteosarcomas, synovial sarcomas, liposarcomas, malignan t schwannomas, and other types of tumors, as well as 11 benign tumors, beta -Catenin-activating missense mutations were found in two malignant tumors. One found in MFH occurred at codon 45 and caused an amino acid substitution from serine (one of the GSK3 beta-targeted phosphorylation sites) to pheny lalanine. The other, detected in synovial sarcoma at codon 32, resulted in an amino acid change from aspartic acid (located adjacent to the phosphoryl ation target, serine, encoded by codon 33) to tyrosine, Furthermore, we fou nd accumulation of beta-catenin by western-blotting analysis in 12 of 19 ma lignant tumors in which we found no mutation involving exon 3, Our results suggested the possible involvement of beta-catenin activation, by beta-cate nin gene mutation or alteration of other factor(s), in the formation and/or progression of various types of bone and soft-tissue tumors.