Abnormal structure and expression of PTEN/MMAC1 gene in human uterine cancers

The PTEN/MMAC1 gene, located on human chromosome 10q23, has recently been i mplicated as a candidate tumor suppressor gene in human cancers. In the pre sent study, 12 uterine cancer cell lines and 87 uterine cancers of various grades and histological type were analyzed for PTEN/MMAC1 gene. Three of 44 endometrial carcinoma (7%) showed no PTEN/MMAC1 mRNA expression by RT-PCR analysis. Sequencing analysis of entire coding region of PTEN/MMAC1 gene re vealed mutations in three of six endometrial cancer cell lines (50%) and 17 of 44 endometrial cancer tissues (39%). In contrast, for cervical cancers, only one of six cancer cell lines (2%) showed mutation, and one of 43 canc er tissues (2%) had an abnormality. Overall, 36% of the abnormal spots were located in exon 5, 24% were in exon 8, 16% were in exon 3, and 8% were in exon 6, and single cases of abnormality were found in exons 1, 4, and 7. Ou r results revealed that, in total, 60% of abnormalities were clustered in e xons 5 and 8. Exon 5 is a functional domain of the PEN/MMAC1 gene, and ther efore, abnormalities in this region may be important for loss of PTEN/MMAC1 gene function. Finally, we found a high frequency of PTEN/MMAC1 gene abnor malities in endometrial carcinomas but a low frequency in cervical carcinom as. These findings suggest that disruption of PTEN/MMAC1 by mutation or abs ence of expression may contribute to the pathogenesis or neoplastic evoluti on in a large proportion of endometrial carcinomas but in a small proportio n of cervical carcinomas. (C) 2000 Wiley-Liss, Inc.