DNA Methylation In Primary Sporadic Ovarian Cancers

Objective It is very significant to set up early detection for ovarian cancer's early diagnose and improvement of patients' prognosis.Our research emphasizes on the effect of aberrant methylation of CpG islands of tumor suppressor 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 deciding early diagnosis signs.Methods We determined the frequency of aberrant promoter methylation of 6 genes in 76 primary ovarian cancer samples and 21 normal fresh ovarian tissues by using methylation-specific-PCR(MSP). And we detected the LOH of 3 genes:p15,p19,p73 by microsatellite polymorphism signs: D9S1748 and D1S2734.Results Genes participating in cell-cycling adjust show high frequences of methylation : pl9(52.6%), Rbl(41.8%), FHIT(39.3%), pl5(29.8%), COX-2 (23.3%), p73(21.7%).Methylation in ovarian cancer is not associated with clinical staging, differentiation grade, age and tissue-type. And there is no significantly difference between malignant and low malignant tissues. A total of 88.5% of the ovarian cancers have methylation of at least one of these genes, 57.4% of the ovarian cancers have two genes methylated, 24.6% of the ovarian cancers have three genes methylated, and 6.6% of the ovarian cancers have four genes methylated. Methylation of these genes are not correlated with histology type, clinical stage and celldifferentiation of the patients.Paracarcinoma tissues also show DNA methylation: FHIT(51.7%), pl9(35.5%), pl5(27.9%), Rbl(27.3%), p73(17.9%), COX-2 (0%).There is no DNA methylation in normal ovarian tissues.High frequence of LOH:45.2%, 59.1%. And there is no relationship between DNA methylation and LOH.Conclusions?Genes which participate in cell cycle regulation show high methylation frequence of CpG islands. We can presume that aberrant methylation of CpG islands occured in tumor is one method for loss of gene function, which lead to unconfmed growth of tumor cells. We conclude that methylation of TSG is a frequent event in ovarian cancers and is an important mechanism for loss of expression of these genes.?It is very significant for early detection of ovarian cancer's early diagnose and improvement of patients' prognosis. Methylation of TSG commences during ovarian cancer carcinogenesis and may represent a marker for risk assessment.?Considering the two hits theory, DNA methylation and loss of heterozygosity forms two hits , leading the gene silencing and tumor's occurrence.