Prognostic And Diagnostic Significance Of DNA Methylation Patterns In High Grade Serous Ovarian Cancer

Publisher:
Academic Press Inc Elsevier Science
Publication Type:
Journal Article
Citation:
Gynecologic Oncology, 2012, 124 (3), pp. 582 - 588
Issue Date:
2012-01
Full metadata record
Files in This Item:
Filename Description Size
Thumbnail2013005848OK.pdf350.7 kB
Adobe PDF
Objective. Altered DNA methylation patterns hold promise as cancer biomarkers. In this study we selected a panel of genes which are commonly methylated in a variety of cancers to evaluate their potential application as biomarkers for prognosis and diagnosis in high grade serous ovarian carcinoma (HGSOC); the most common and lethal subtype of ovarian cancer. Methods. The methylation patterns of 10 genes (BRCA1, EN1, DLEC1, HOXA9, RASSF1A, GATA4, GATA5, HSULF1, CDH1, SFN) were examined and compared in a cohort of 80 primary HGSOC and 12 benign ovarian surface epithelium (USE) samples using methylation-specific headloop suppression PCR. Results. The genes were variably methylated in primary HGSOC, with HOXA9 methylation observed in 95% of cases. Most genes were rarely methylated in benign USE, with the exception of SFN which was methylated in all HGSOC and benign USE samples examined. Methylation of DLEC1 was associated with disease recurrence, independent of tumor stage and suboptimal surgical debulking (HR 3.5 (95% CI:1.10-11.07), p=0.033). A combination of the methylation status of HOXA9 and EN1 could discriminate HGSOC from benign USE with a sensitivity of 98.8% and a specificity of 91.7%, which increased to 100% sensitivity with no loss of specificity when pre-operative CA125 levels were also incorporated. Conclusions. This study provides further evidence to support the feasibility of detecting altered DNA methylation patterns as a potential diagnostic and prognostic approach for HGSOC.
Please use this identifier to cite or link to this item: