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WT1 and WT1-AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma
Article first published online: 30 AUG 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 9, pages 1924–1930, 1 November 2005
How to Cite
Kaneuchi, M., Sasaki, M., Tanaka, Y., Shiina, H., Yamada, H., Yamamoto, R., Sakuragi, N., Enokida, H., Verma, M. and Dahiya, R. (2005), WT1 and WT1-AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma. Cancer, 104: 1924–1930. doi: 10.1002/cncr.21397
- Issue published online: 17 OCT 2005
- Article first published online: 30 AUG 2005
- Manuscript Accepted: 3 DEC 2004
- Manuscript Revised: 17 NOV 2004
- Manuscript Received: 13 AUG 2004
- National Institutes of Health and Veterans' Administration Research Enhancement Award Program (REAP) award and Merit Review grants. Grant Numbers: RO1AG21418, RO1CA101844, T32DK07790
- Wilms tumor suppressor 1 gene;
- WT1 antisense;
- ovarian carcinoma;
- cancers of the ovary
Ovarian clear cell adenocarcinoma is associated with one of the poorest prognoses among human epithelial ovarian cancers. The authors hypothesized that Wilms tumor suppressor 1 gene (WT1) sense and antisense (WT1-AS) expression and their promoter methylation status could characterize ovarian clear cell adenocarcinoma from ovarian serous adenocarcinoma.
To test this hypothesis, ovarian cancer cell lines and 42 cancer tissues (17 clear cell and 25 serous adenocarcinoma) were analyzed for expression and methylation of WT1 and WT1-AS genes.
These experiments demonstrated that all serous adenocarcinoma tissues expressed both WT1 and WT1-AS genes, although expression of these genes was lacking in clear cell adenocarcinoma. The WT1 and WT1-AS promoter were significantly methylated in clear cell adenocarcinoma (88.2% and 88.2%, respectively) compared with serous adenocarcinoma (24.0% and 20.0%, respectively). Significant correlation between methylation and mRNA expression status was observed for each gene. Also in agreement with these data, WT1 and WT1-AS negative ovarian cancer cell lines reexpressed these genes after treatment with the demethylating agent, 5-aza-2′-deoxycytidine.
The current study shows that CpG hypermethylation is an important mechanism of WT1 and WT1-AS gene inactivation in ovarian clear cell adenocarcinoma. This is the first report that has demonstrated differential expression and methylation of WT1-AS in ovarian clear cell and serous adenocarcinomas. This study presents new molecular characterizations between these two types of adenocarcinoma and may provide insight as to why clear cell adenocarcinoma has a poorer prognosis than serous adenocarcinoma of the ovary. Cancer 2005. © 2005 American Cancer Society.