Abstract
Aberrant methylation of gene promoter regions is one of the mechanisms for inactivation of tumor suppressor genes in human malignancies. In this study, the methylation pattern of 24 tumor suppressor genes was analyzed in 75 samples of ovarian cancer using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Of the 24 tumor suppressor genes examined, aberrant methylation was observed in 17. The three most frequently methylated genes were CDKN2B, CDH13 and RASSF1, followed by ESR1 and MLH1. Methylation frequencies ranged from 1.3% for CDKN2A, RARβ, CASP8, VHL and TP73 to 24% for CDKN2B. The corresponding normal DNA from each patient was also investigated. Methylation was detected in tumors, although not in normal tissues, with the exception of two samples, indicating aberrant methylation in tumors. Clear cell carcinoma samples exhibited a higher frequency of CDKN2B promoter hypermethylation compared to those of other histological types (P=0.05). Our data indicate that methylation of the CDKN2B gene is a frequent event in ovarian carcinogenesis and that analysis of only three genes is sufficient to detect the presence of methylation in 35% of ovarian cancer cases. However, more studies using a much larger sample size are needed to define the potential role of DNA methylation as a marker for ovarian cancer.
Highlights
Ovarian cancer is the most lethal tumor of the female genital tract and the second most frequent gynecological cancer [1]
Promoter regions from a total of 24 tumor suppressor genes were analyzed for methylation of CpG islands in the tumors and adjacent normal tissues of 75 ovarian cancer cases
Methylation of the ATM, HIC1, CDKN1B, PTEN and FHIT genes was not detected in any tumor sample, whereas low frequencies were observed for the DAPK1 (3 samples), CHFR, IGSF4, GSTP1 (2 samples), CDKN2A, RARβ, CASP8, VHL and TP73 (1 sample) genes
Summary
Ovarian cancer is the most lethal tumor of the female genital tract and the second most frequent gynecological cancer [1]. 1.5% of females develop ovarian cancer in their lifetime. As ovarian cancer has few symptoms in its course, most cases are diagnosed in the late stages. If diagnosed during the early stages, most cases are curable. A better understanding of the molecular mechanisms responsible for ovarian cancer development and progression is likely to aid the improvement of the diagnosis and treatment of the disease
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