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

被引：63

作者：

Giannopoulou, Lydia ^{[1
]}

Chebouti, Issam ^{[2
]}

Pavlakis, Kitty ^{[3
]}

Kasimir-Bauer, Sabine ^{[2
]}

Lianidou, Evi S. ^{[1
]}

机构：

[1] Univ Athens, Dept Chem, Analyt Chem Lab, Anal Circulating Tumor Cells Lab, Univ Campus, GR-15771 Athens, Greece

[2] Univ Duisburg Essen, Univ Hosp Essen, Dept Gynecol & Obstet, D-45122 Essen, Germany

[3] IASO Womens Hosp, Dept Pathol, Athens 15123, Greece

来源：

ONCOTARGET | 2017年 / 8卷 / 13期

关键词：

circulating tumor DNA; RASSF1A; high-grade serous ovarian cancer; methylation specific PCR; high resolution melting analysis; BREAST; HYPERMETHYLATION; PLASMA; GENE; LUNG; BIOMARKERS; DIAGNOSIS; PLATINUM; PATTERNS; THERAPY;

D O I：

10.18632/oncotarget.15249

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：21429 / 21443

页数：15

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