title: Prognostic and diagnostic significance of DNA methylation patterns in high grade serous ovarian cancer.
abstract: 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 (OSE) 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 OSE, with the exception of SFN which was methylated in all HGSOC and benign OSE 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 OSE 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.
authors: Cancer Research Program, Garvan Institute of Medical Research, Sydney NSW 2010, Australia.
authors: Céline
authors: C
authors: Montavon
authors: Brian S
authors: BS
authors: Gloss
authors: Kristina
authors: K
authors: Warton
authors: Caroline A
authors: CA
authors: Barton
authors: Aaron L
authors: AL
authors: Statham
authors: James P
authors: JP
authors: Scurry
authors: Bruce
authors: B
authors: Tabor
authors: Tuan V
authors: TV
authors: Nguyen
authors: Wenja
authors: W
authors: Qu
authors: Goli
authors: G
authors: Samimi
authors: Neville F
authors: NF
authors: Hacker
authors: Robert L
authors: RL
authors: Sutherland
authors: Susan J
authors: SJ
authors: Clark
authors: Philippa M
authors: PM
authors: O'Brien
mesh_terms: D015331:Cohort Studies; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C119064:DLEC1 protein, human; C513076:EN1 protein, human; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; C097899:homeobox protein HOXA9