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KMID : 0880520090450010047
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Chonnam Medical Journal
2009 Volume.45 No. 1 p.47 ~ p.54
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The Role of PTEN Mutation in the Development of Endometrial Carcinoma
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Choi Yoo-Duk
Kim Sung-Sun
Park Chang-Soo
Nam Jong-Hee
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Abstract
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Over the past 2 decades, the tendency has been to classify endometrial carcinoma into 2 different types. Type I tumors (about 80%) are endometrioid carcinomas, are often preceded by complex and atypical hyperplasia, and are associated with estrogen stimulation. Type II tumors (about 10%) are nonendometrioid carcinomas that arise occasionally from precancerous lesions that develop in atrophic endometria. It has been found that the molecular alterations of endometrioid carcinomas, including defects in DNA-mismatch repair and mutations in PTEN (phosphatase and tension homologue deleted in chromosome ten), K-ras, and beta-catenin, are different from those of the nonendometrioid carcinomas. In this study, we analyzed the PTEN mutation by direct DNA sequencing of the endometrial hyperplasia and endometrioid carcinoma in order to investigate the molecular carcinogenesis of Type I endometrial carcinoma. PTEN mutations were detected in 14 (37.8%) of 37 carcinomas, including 8 cases (21.6%) in exon 5, 1 case (2.7%) in exon 6, 5 cases (13.5%) in exon 7, and 3 cases (8.1%) in exon 8. The most frequent site of PTEN mutation was codon 130 on exon 5, which encodes the tyrosine phosphatase catalytic domain. The PTEN mutation was not associated with histologic grade, depth of invasion, or clinical stage. PTEN mutations were also shown in 3 cases (15.8%) of 19 typical endometrial hyperplasias and in 6 cases (28.6%) of 21 atypical endometrial hyperplasias. These results suggest that PTEN is an important target gene in the development of type I endometrial carcinomas and that the presence of PTEN mutations in typical and atypical endometrial hyperplasia suggest that PTEN mutations would occur as early events in the process of type I endometrial carcinogenesis.
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KEYWORD
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Endometrium, Hyperplasia, Carcinoma, PTEN gene, Mutation
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