Aberrant promoter methylation of the RASSF1A and APC genes in epithelial ovarian carcinoma development

Bhagat, Rahul; Chadaga, Shilpa; Premalata, C S; Ramesh, Gayathri; Ramesh, C.; Pallavi, V. R.; Krishnamoorthy, Lakshmi

doi:10.1007/s13402-012-0106-4

Cited by 29 publications

(30 citation statements)

References 32 publications

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“…RASSF1A acts as a tumor suppressor gene in the RAS pathway and can regulate proliferation, induce apoptosis, and bind to and stabilize microtubules . Previous studies showed that the frequency of promoter hypermethylation of RASSF1A in ovarian carcinomas was 40-58% (Yoon et al, 2001;Bhagat et al, 2012). In our study, epithelial ovarian cancers exhibited RASSF1A gene promoter methylation frequencies of 48.6% (17/35).…”

Section: Discussionsupporting

confidence: 57%

“…Ibanez de Caceres et al (2004) reported a significant correlation between methylation status, tumor grade, CA125 levels, and stage in ovarian cancer. However, we found that the methylation status of RASSF1A was not related to age, grade, stage, histological type, ascites, and CA125, which was similar to the results of Bhagat et al (2012). Homeodomain-containing genes encode transcriptional factors that function during embryonic development to control patterning, differentiation, and proliferation (Gorski and Walsh, 2003).…”

Section: Discussionsupporting

confidence: 49%

“…Based on published studies, the 3 genes RASSF1A, OPCML, and HOXA9 were selected because they show a high frequency of methylation in EOC and no methylation in normal tissues (Rathi et al, 2002;Teodoridis et al, 2005;Wu et al, 2007;Liggett et al, 2011). In EOC, inactivation of the RASSF1A, OPCML, and HOXA9 gene promoters was reported to be related to carcinogenesis or early cancer (Sellar et al, 2003;Montavon et al, 2012;Bhagat et al, 2012;Zhang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that determining the methylation status of a panel of genes, rather than an individual gene, will result in more sensitive and specific diagnosis (Montavon et al, 2012;Bhagat et al, 2012). We developed a cationic conjugated polymer (CCP)-based fluorescence resonance energy transfer (FRET) method for detecting the methylation levels of Ras association domain family 1 isoform A (RASSF1A), opioid-binding protein/cell adhesion molecule (OPCML), and homeobox A9 (HOXA9) of EOCs and associated analysis of DNA methylation (Zhang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Xing¹,

Tang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. DNA methylation plays an important role in carcinogenesis and cancer development. In this study, we examined gene methylation in epithelial ovarian cancer (EOC) using cationic conjugated polymer (CCP)-based fluorescence resonance energy transfer (FRET) to evaluate the application of cumulative methylation alternations of genes associated with cancer antigen 125 for early cancer diagnosis. The methylation status of 3 genes (Ras association domain family 1 isoform A, RASSF1A; opioid-binding protein/cell adhesion molecule, OPCML; homeobox A9, HOXA9) were examined and compared in 35 EOC samples and 11 normal ovarian tissue samples using CCP-based FRET. Gene methylation levels were clustered into 3 sections and assigned a value; values for the 3 genes were summed. Although methylation of the OPCML gene was significantly associated with stage, histological types, grade, and ascites and that of RASSF1A and HOXA9 was not, the sum for the 3 genes was significantly associated with stage and ascites. The sum showed higher sensitivity (85.7%) and specificity (100%) for discriminating EOC from normal ovarian tissues than did the methylation status of RASSF1A, OPCML, and HOXA9

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Section: Discussionsupporting

confidence: 57%

Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Xing¹,

Tang

et al. 2015

Genet. Mol. Res.

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“…Methylation of the RASSF1A promoter is described as an early and frequent event in tumorigenesis, thus RASSF1A can serve as a useful diagnostic marker in cancer screening (Dammann et al, 2000;Dammann et al, 2001;Liu WJ et al, 2013), including ovarian cancer (Agathanggelous et al, 2001;Yoon et al, 2001;Rathi et al, 2002;Ibanez et al, 2004;Makarla et al, 2005;Choi et al, 2006;Ma et al, 2009;BonDurant et al, 2011;Bhagat et al, 2012).…”

Section: Aberrant Methylation Of Rassf2a In Tumors and Plasma Of Patimentioning

confidence: 99%

Aberrant Methylation of RASSF2A in Tumors and Plasma of Patients with Epithelial Ovarian Cancer

Zhang²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The role of DNA methylation in ovarian cancer chemoresistance: A narrative review

Song

Artibani

2023

Health Science Reports

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Background and Aims: Ovarian cancer (OC) is the most lethal gynecological cancer.In 2018, it was responsible for over 180,000 deaths worldwide. The high mortality rate is the culmination of a lack of early diagnosis and high rates of chemotherapy resistance, which is synonymous with disease recurrence. Over the last two decades, an increasingly significant role of epigenetic mechanisms, in particular DNA methylation, has emerged. This review will discuss several of the most significant genes whose hypo/hypermethylation profiles are associated with chemoresistance.Aside from functionally elucidating and evaluating these epimutations, this review will discuss recent trials of DNA methyltransferase inhibitors (DNMTi). Finally, we will propose future directions that could enhance the feasibility of utilizing these candidate epimutations as clinical biomarkers.Methods: To perform this review, a comprehensive literature search based on our keywords was conducted across the online databases PubMed and Google Scholar for identifying relevant studies published up until August 2022.Results: Epimutations affecting MLH1, MSH2, and Ras-association domain family 1 isoform A (DNA damage repair and apoptosis); ATP-binding cassette subfamily B member 1 and methylation-controlled J (drug export); secreted frizzled-related proteins (Wnt/β-catenin signaling), neurocalcin delta (calcium and G protein-coupled receptor signaling), and zinc finger protein 671 all have potential as biomarkers for chemoresistance. However, specific uncertainties relating to these epimutations include histotype-specific differences, intrinsic versus acquired chemoresistance, and the interplay with complete surgical debulking. DNMTi for chemoresistant OC patients has shown some promise; however, issues surrounding their efficacy and dose-limiting toxicities remain; a personalized approach is required to maximize their effectiveness. Conclusion:Establishing a panel of aberrantly methylated chemoresistance-related genes to predict chemoresponsiveness and patients' suitability to DNMTi could significantly reduce OC recurrence, while improving DNMTi therapy viability. To achieve this, a large-scale prospective genome-wide DNA methylation profile study

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Aberrant promoter methylation of the RASSF1A and APC genes in epithelial ovarian carcinoma development

Abstract: The observed aberrant methylation frequencies of the RASSF1A and APC gene promoters indicate that an accumulation of epigenetic events at these specific TSG promoters may be associated with the malignant transformation of benign cystadenomas and LMP tumours to carcinomas.

Cited by 29 publications

References 32 publications

Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Cumulative methylation alternations of gene promoters and protein markers for diagnosis of epithelial ovarian cancer

Aberrant Methylation of RASSF2A in Tumors and Plasma of Patients with Epithelial Ovarian Cancer

The role of DNA methylation in ovarian cancer chemoresistance: A narrative review

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