RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time meth...

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Bibliographic Details
Published in:Oncotarget 2017-03, Vol.8 (13), p.21429-21443
Main Authors: Giannopoulou, Lydia, Chebouti, Issam, Pavlakis, Kitty, Kasimir-Bauer, Sabine, Lianidou, Evi S
Format: Article
Language:English
Subjects:
Adult
Aged
Biomarkers, Tumor - genetics
Cystadenocarcinoma, Serous - genetics
Cystadenocarcinoma, Serous - mortality
Disease-Free Survival
DNA Methylation - genetics
DNA, Neoplasm - blood
Female
Humans
Kaplan-Meier Estimate
Middle Aged
Ovarian Neoplasms - genetics
Ovarian Neoplasms - mortality
Prognosis
Promoter Regions, Genetic - genetics
Proportional Hazards Models
Real-Time Polymerase Chain Reaction
Research Paper
Tumor Suppressor Proteins - genetics
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Summary:The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.15249