Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors

Liggett, Thomas; Melnikov, Anatoliy A.; Yi, Qilong; Replogle, Charles; Hu, Wei; Rotmensch, Jacob; Kamat, Aparna A.; Sood, Anil K.; Levenson, Victor

doi:10.1016/j.ygyno.2010.09.019

Cited by 99 publications

(84 citation statements)

References 35 publications

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“…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%

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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: Discussionmentioning

confidence: 99%

“…Recent studies have shown that aberrant DNA methylation, which typically occurs before patients develop clinical manifestations and radiographic evidence, can be detected in cellfree serum (Vlassov et al, 2010;Liggett et al, 2011;Zhang et al, 2013). The amount of available cell-free serum DNA is often very low.…”

Section: Discussionmentioning

confidence: 99%

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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“…The same group used this assay in three cohorts of serous ovarian cancer patients, benign ovarian disease patients and healthy controls. Liggett et al [63] now reported the distinctive promoter methylation of all three groups according to the methylation status of six selected genes.…”

Section: Aberrant Methylationmentioning

confidence: 97%

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

Giannopoulou

Kasimir‐Bauer

Lianidou

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Ovarian cancer remains the most lethal disease among gynecological malignancies despite the plethora of research studies during the last decades. The majority of patients are diagnosed in an advanced stage and exhibit resistance to standard chemotherapy. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) represent the main liquid biopsy approaches that offer a minimally invasive sample collection. Both have shown a diagnostic, prognostic and predictive value in many types of solid malignancies and recent studies attempted to shed light on their role in ovarian cancer. This review is mainly focused on the clinical value of both CTCs and ctDNA in ovarian cancer and, more specifically, on their potential as diagnostic, prognostic and predictive tumor biomarkers.

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“…As in the early diagnosis of ovarian carcinoma, it was reported that the detection rates of OPCML methylation in the serum and cancerous tissues of patients with ovarian carcinoma were 80.0% and 86.7%, respectively, indicating that detecting serum free DNA OPCML methylation level could be an effective method for the diagnosis of ovarian carcinoma (Zhou et al, 2014). In addition, Liggett et al verified that the sensitivity and specificity of serum free DNA RASSF1A and PGR-PROX gene methylation were 80.0% and 73.3% respectively in identifying benign and malignant tumors (Liggett et al, 2011).…”

Section: Discussionmentioning

confidence: 98%

Application of Multiplex Nested Methylated Specific PCR in Early Diagnosis of Epithelial Ovarian Cancer

Bi¹,

Yu²,

Yang³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Objective: To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). Materials and Methods: Serum and fresh tissue samples were collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes. Methylation levels of tissues were assessed by multiplex nested methylated specific PCR, the results being compared with those for carcinoma antigen 125 (CA125). Results: The serum free deoxyribose nucleic acid (DNA) methylation spectrum of EOC patients was completely contained in the DNA spectrum of cancer tissues, providing an accurate reflection of tumor DNA methylation conditions. Serum levels of CA125 and free DNA methylation in the EOC group were evidently higher than those in benign lesion and control groups (p<0.05). Patients with early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05), but there was no significant difference in free DNA methylation (p>0.05). The sensitivity, specificity and positive predicative value (PPV) of multiplex nested methylated specific PCR were significantly higher for detection of all patients and those with early EOC than those for CA125 (p<0.05). In the detection of patients with advanced EOC, the PPV of CA125 detection was obviously lower than that of multiplex nested methylated specific PCR (p>0.05), but there was no significant difference in sensitivity (p>0.05). Conclusions: Serum free DNA methylation can be used as a biological marker for EOC and multiplex nested methylated specific PCR should be considered for early diagnosis since it can accurately determine tumor methylation conditions.

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Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors

Cited by 99 publications

References 35 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

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA

Application of Multiplex Nested Methylated Specific PCR in Early Diagnosis of Epithelial Ovarian Cancer

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