Abstract
Ovarian cancer is the most lethal gynecological malignancy, with typically late diagnosis. Altered DNA methylation of tumor suppressor gene promoters probably plays a relevant role in ovarian carcinogenesis and frequently occurs as an early event in the development of different types of cancer including ovarian carcinoma. GATA4 methylation has been reported in a variety of human cancers. The aim of this study was to investigate promoter methylation of the GATA4 gene in ovarian cancer by comparison with that in normal ovarian tissue. To search for promoter methylation of the GATA4 gene we used MSP (methylation-specific PCR) to compare the methylation status in 67 tissue samples of ovarian cancer with that in 40 control samples. In our study, methylation-specific PCR revealed GATA4 promoter methylation in 21 of 67 specimens with ovarian cancer (31.3%), and in none of the control ovarian tissue samples. These results confirm that methylation in the GATA4 promoter region could play an important role in ovarian carcinogenesis, and show new loci which are highly methylated only in ovarian cancer samples and which are associated predominantly with the endometrioid type of ovarian carcinoma.
Highlights
Ovarian cancer is the leading cause of death from gynecologic tumors due to its aggressive nature and the fact that the majority of patients are diagnosed in the advanced stages of the disease
GATA4 showed statistically significant higher methylation in the endometrioid tumor type compared with the serous histological type of ovarian carcinoma
Loss of GATA4 expression has been frequently observed in ovarian cancer[13,14,15]
Summary
Ovarian cancer is the leading cause of death from gynecologic tumors due to its aggressive nature and the fact that the majority of patients are diagnosed in the advanced stages of the disease. It has generally been assumed that if ovarian cancer could be diagnosed at an early stage, this would result in a significant improvement in survival[1]. The hypothesis has been proposed that repeated wound repair after ovulation may contribute to the ovarian tumorigenesis processes[2]. Both genetic and epigenetic changes contribute to malignant transformation and progression. Aberrant methylation of normally unmethylated CpG islands, located in the 5 ́ promoter region of genes, has been associated with transcriptional inactivation of several genes in human cancer, and can serve as an alternative to mutational inactivation[3]. It has been suggested that DNA methylation profiles may be useful biomarkers and may serve as a potential target for development of antimethylation therapeutic strategies[4]
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