MUTATION OF THE PTEN TUMOR-SUPPRESSOR GENE IN ENDOMETRIAL HYPERPLASIAS

Mutation and deletion of the PTEN tumor suppressor gene occurs in abou t 40% of endometrial carcinomas. The purpose of this study was to dete rmine whether PTEN mutations also are present in endometrial hyperplas ias, which are premalignant precursors of invasive endometrial adenoca rcinomas. Genomic DNA from 51 endometrial hyperplasias was extracted f rom paraffin blocks, and PCR was used to amplify the nine exons of the PTEN gene, These products were screened using single-strand conformat ion analysis, and variant bands were sequenced, Somatic mutations in t he PTEN gene were seen in 10 of 51 cases (20%), and two mutations were found in one case. An identical 4-bp deletion in exon 8 was seen in t hree cases, and 8 of 11 PTEN mutations predicted truncated protein pro ducts. There was no higher frequency of PTEN mutations in endometrial hyperplasias with atypia (6 of 32; 19%) relative to those without atyp ia (4 of 19; 21%). These data suggest that inactivation of the PTEN tu mor suppressor gene is an early event in the development of some endom etrial cancers.