title: Aberrant methylation of RASSF2A in tumors and plasma of patients with epithelial ovarian cancer.
abstract: OBJECTIVE
  The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated by promoter hypermethylation in many cancers. The current study was performed to evaluate the methylation status of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expression and clinicopathologic characteristics.
  
  
  METHODS
  We detected methylation of the RASSF2A gene in tissues and corresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 with normal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expression of mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2'-deoxycytidine (5-aza- dC).
  
  
  RESULTS
  RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrant methylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas such hypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression of RASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylated group (p<0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in the Skov3 cell line.
  
  
  CONCLUSIONS
  Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be a valuable molecular marker for the early detection of EOC.
authors.affiliation: Department of Gynecology and Obstetrics, Qilu Hospital, Shandong University, Jinan, China E-mail : peishuliu0531@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Ma
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Ma
authors.forename: Pei-Shu
authors.initials: PS
authors.lastname: Liu
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D000077209:Decitabine; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C425300:RASSF2 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine