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Departments of Obstetrics and Gynecology/Division of Gynecologic Oncology [G. L. M., A. B., P. A. F.], Surgery [C. G., P. A. F.], Medicine [H. S.], and Pathology [R. C. B.], Duke University Medical Center, Durham, North Carolina 27710, and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [J. I. R., J. C. B.]
Mutation and deletion of the PTEN tumor suppressor gene occurs in about 40% of endometrial carcinomas. The purpose of this study was to determine whether PTEN mutations also are present in endometrial hyperplasias, which are premalignant precursors of invasive endometrial adenocarcinomas. Genomic DNA from 51 endometrial hyperplasias was extracted from paraffin blocks, and PCR was used to amplify the nine exons of the PTEN gene. These products were screened using single-strand conformation analysis, and variant bands were sequenced. Somatic mutations in the 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 three cases, and 8 of 11 PTEN mutations predicted truncated protein products. There was no higher frequency of PTEN mutations in endometrial hyperplasias with atypia (6 of 32; 19%) relative to those without atypia (4 of 19; 21%). These data suggest that inactivation of the PTEN tumor suppressor gene is an early event in the development of some endometrial cancers.
1 Supported in part by the Duke University Specialized Programs of Research Excellence in Breast Cancer from the National Cancer Institute.
2 To whom requests for reprints should be addressed, at Division of Gynecologic Oncology, Duke University Medical Center, Box 3079, Durham, NC 27710. Phone: (919) 684-3765; Fax: (919) 684-8719.
Received 3/ 5/98. Accepted 4/28/98.
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