title: Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation.
abstract: OBJECTIVE
  To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Medical center.
  
  
  METHODS
  Twenty-two epithelial ovarian cancer and six normal ovary tissues.
  
  
  METHODS
  Mutation and altered expression of hSRBC gene.
  
  
  METHODS
  hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing.
  
  
  RESULTS
  Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2'-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level.
  
  
  CONCLUSIONS
  Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.
authors.affiliation: Department of Obstetrics and Gynecology, East-West Neo Medical Center, Kyung Hee University, #149 Sangil-Dong, Gangdong-Gu, Seoul, Korea.
authors.forename: Seo-Yun
authors.initials: SY
authors.lastname: Tong
authors.forename: Kyung-Do
authors.initials: KD
authors.lastname: Ki
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Kang
authors.forename: Tae-Kyu
authors.initials: TK
authors.lastname: Ha
authors.forename: Seong-In
authors.initials: SI
authors.lastname: Chung
authors.forename: Sung-Gil
authors.initials: SG
authors.lastname: Chi
authors.forename: Seon-Kyung
authors.initials: SK
authors.lastname: Lee
mesh_terms: D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005629:Frozen Sections; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C505360:CAVIN3 protein, human; D047908:Intracellular Signaling Peptides and Proteins