Abstract

DNA methylation is considered a promising biomarkers for diagnosis of cancer in general and of ovarian cancer in particular. In our study, we validated the accuracy of methylation specific polymerase chain reaction (MSP) to analyze the methylation pattern of BRCA1, RASSF1A and ER in 59 and 10 Vietnamese patients with epithelial ovarian cancer (EOC) and benign ovarian tumors, respectively. We found methylation of BRCA1, RASSF1A and ER in 11/59 (18.6%), 40/59 (67.8%) and 15/59 (25.4%) of EOC cases, while methylation of BRCA1 was only detected in 2/10 (20%) benign ovarian patients. Forty five out of the 59 EOCs (78%) demonstrated methylation at one or more genes. The methylation frequency of RASSF1A was significantly associated with EOC (p<0.0005). No significant association was observed between methylation status of these genes and the clinical and pathological parameters of tumors collected from Vietnamese women suffering from ovarian cancer.

Highlights

  • Ovarian cancer is the leading cause of death and the second most common cancer among women with gynaecological cancers (Siegel et al, 2012)

  • We validated the accuracy of methylation specific polymerase chain reaction (MSP) to analyze the methylation pattern of Breast cancer 1 (BRCA1), RASSF1A and estrogen receptor α (ER) in 59 and 10 Vietnamese patients with epithelial ovarian cancer (EOC) and benign ovarian tumors, respectively

  • Among a large number of genes that have been identified as hypermethylated in EOC, three genes BRCA1, RASSF1A (RAS-association domain family member 1) and ER were extensively studied because (i) methylation of BRCA1 occurs only in breast and ovarian cancers (Esteller et al, 2001), (ii) methylation of RASSF1A is frequently associated with the early stage of many primary tumors including ovarian one (Agathanggelou et al, 2001), and (iii) methylation of ER is closely involved in ER signaling that plays a key role in hormonal cancer progression (Mann et al, 2011)

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Summary

Introduction

Ovarian cancer is the leading cause of death and the second most common cancer among women with gynaecological cancers (Siegel et al, 2012). Among a large number of genes that have been identified as hypermethylated in EOC, three genes BRCA1 (breast cancer 1, early onset), RASSF1A (RAS-association domain family member 1) and ER (estrogen receptor 1) were extensively studied because (i) methylation of BRCA1 occurs only in breast and ovarian cancers (Esteller et al, 2001), (ii) methylation of RASSF1A is frequently associated with the early stage of many primary tumors including ovarian one (Agathanggelou et al, 2001), and (iii) methylation of ER is closely involved in ER signaling that plays a key role in hormonal cancer progression (Mann et al, 2011). Specific methylation of one panel of six genes was detected in the serum or plasma of ovarian cancer patients with 100% specificity and 82% sensitivity (de Caceres et al, 2004)

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