MTAP gene deletion in endometrial cancer

Abstract

A gene (MTAP) that encodes the enzyme 5'-deoxy-5'-methylthioadenosine (MTA) phosphorylase has been identified on chromosome 9p21 and cloned. The substrate of this enzyme, MTA, inhibits aminopropyltransferases that synthesize polyamines from putrescine and decarboxylated S-adenosylmethionine. This enzyme normally cleaves MTA to adenine and 5'-methylthioribose-1-phosphate, which are recycled to adenine nucleotides and methionine, respectively. Cancers with deletions of the MTAP gene may be especially susceptible to chemotherapeutic regimes which interfere with purine or methionine utilization. The purpose of this study was to determine deletion of the MTAP gene in endometrial cancer using a polymerase chain reaction-based method. Therefore, 50 endometrial adenocarcinomas were studied. Partial or total deletions of the MTAP gene were detected in 7 (14%) of these cancers. There were no significant relationships between gene deletion and patient age, pathological grade or clinical stage (p > 0.05). The findings indicate that deletion of the MTAP gene does occur in a subgroup of endometrial cancer. The present work may be extended to the development of molecular diagnosis of MTAP gene deletion in other cancers and assist in selecting appropriate chemotherapy.