Methylation of tumor suppressor genes in ovarian cancer

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.

Mitomycin-C suppresses mucus secretion in an ileal neobladder rat model

“…Previous studies have indicated that the use of enzymes or a combination of acid hydrolysis can significantly reduce the viscosity of mucus (14,15). The results of the present study demonstrated that experimental dosages of 0.6 and 0.4 mg/ml MMC can decrease the level of sialic acid in the urine and the number of mature goblet cells, with the effect dose-dependent.…”

Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor

“…Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported (provided by RefSeq, Jul 2008). Methylation of CDKN2B has been found in several cancer types including laryngeal squamous cell carcinoma, acute myeloid leukemia, and in ovarian cancer, where the presence of methylation in the CDKN2B gene was present mainly in clear cell carcinoma [34][35][36] . MUS81 (Structure-Specific Endonuclease Subunit) is a protein coding gene.…”

Methylation Profile of BRCA1, RASSF1A and ER in Vietnamese Women with Ovarian Cancer

“…In addition, no correlations between the methylation levels of BRCA1 and ER that were determined by MSP method and the clinical and pathological parameters of tumors were observed in 215 ovarian cancer patients (Wiley et al, 2006). Moreover, methylation status of BRCA1 and ER determined by MS-MLPA method and that of BRCA1 and RASSF1A determined by head loop PCR showed no association with tumor stages in 75 and 80 ovarian tumors, respectively (Montavon et al, 2012;Ozdemir et al, 2012). It is notable that the correlation between methylation of these genes and clinic-pathological tumor has been reported at the late stage (FIGO III/IV) of ovarian tumors whereas almost all of the examined specimens in our study were in the early stage (FIGO I/II) (Teodoridis et al, 2005;BonDurant et al, 2011).…”