Analysis Of Methylation Of Promoter CpG Island Of Dab2,GATA-4,GATA-5 Genes In Primary Sporadic Ovarian

Objective:Our research emphasizes on the effect of aberrant methylation of CpG islands of Dab2,GATA-4,GATA-5 genes in primary sporadic ovarian cancer's occurrence and development,in order to find the mechanism of ovarian cancer's emergence and try to provide new bases for diagnosis and therapy.Methods:We determined the frenquency of aberrant promoter methylation of Dab2,GATA-4,GATA-5 genes in 41 primary ovarian cancer samples and 15 normal ovarian tissues by using methylation-specific-PCR.Results:Dab2,GATA-4,GATA-5 genes all show methylation in some samples: Dab2(12.12%),GATA-4(51.52%),GATA-5(39.39%), and GATA-4,GATA-5 genes have high frequencies of methylation. With the increased methylation of GATA-4,there was a tendency of increasing methylation of GATA-5.Methylation in ovarian cancer is not associated with clinical staging, differentiation grade,and tissue-type. Borderline tumor of ovary also show DNA methylation :Dab2(21.50%), GATA-4(25.00%), GATA-5(25.00%). A total of 58.53% of the ovarian cancers have methylation of at least one of these genes, 34.15% of the ovarian cancers have two genes methylated,only one case of the ovarian cancers have three genes methylated. There is no DNA methylation in normal ovarian tissues.Conclusion:(1)Dab2,GATA-4,GATA-5 genes show methylation of CpG islands,and GATA-4,GATA-5 show high methlation frenquence .We can presume that aberrant methylation of CpG islands occurred in tumor is one method for loss of gene function, which lead to unconfined growth of tumor cells.We conclude that methylation of gene is a frequent event in ovarian cancers and is an important mechanism for loss of expression of these genes.(2)Coordiantion between the methylation of transcriptional factors and activation of the downstream genes would have great ramifications on cancer progression.Methylation of three genes was observed in low protential malignant tumor. It is very significant for early detection of ovarian cancer's early diagnose(3)Methylation of Dab2 promoter was observed in 4/33 of ovarian cancer cases suggesting that methylation of Dab2 is an infrequent event in ovarian cancer .Frequent loss of Dab2 protein expression can also be attributed to other mechanisms.Another possibility could be post-transcriptional silencing by small interfering molecules,called microRNAs(miRNAs).