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

✍ Scribed by Yuji Yaginuma; Tsuyoshi Yamashita; Takayuki Ishiya; Atsushi Morizaki; Yasuhito Katoh; Tomoaki Takahashi; Hiroaki Hayashi; Mutsuo Ishikawa

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 143 KB
• Volume: 27
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(200002)27:2<110::aid-mc6>3.0.co;2-e

✦ Synopsis

The PTEN/MMAC1 gene, located on human chromosome 10q23, has recently been implicated as a candidate tumor suppressor gene in human cancers. In the present 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 revealed 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 cancer 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. Our results revealed that, in total, 60% of abnormalities were clustered in exons 5 and 8. Exon 5 is a functional domain of the PEN/MMAC1 gene, and therefore, abnormalities in this region may be important for loss of PTEN/ MMAC1 gene function. Finally, we found a high frequency of PTEN/MMAC1 gene abnormalities in endometrial carcinomas but a low frequency in cervical carcinomas. These findings suggest that disruption of PTEN/MMAC1 by mutation or absence of expression may contribute to the pathogenesis or neoplastic evolution in a large proportion of endometrial carcinomas but in a small proportion of cervical carcinomas.