title: Hypermethylation-modulated downregulation of RASSF1A expression is associated with the progression of esophageal cancer.
abstract: OBJECTIVE
  Chromosome 3p21 is an important locus harboring critical tumor suppressor genes (TSGs) implicated in the pathogenesis of multiple tumors including esophageal carcinoma (EC). Aberrant promoter methylation is a fundamental mechanism of inactivation of TSGs in cancer. RASSF1A, a candidate tumor suppressor gene, recently cloned from the lung tumor locus at 3p21.3, is frequently inactivated by hypermethylation of its promoter region in a number of malignancies. We undertook this study to investigate the methylation status of RASSF1A and its significance in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  Real-time RT-PCR and real-time methylation-specific PCR (real-time MSP) were used to detect RASSF1A expression and the methylation status of the RASSF1A promoter, respectively, in 124 primary ESCC tissues.
  
  
  RESULTS
  Hypermethylation, partial methylation and unmethylation of the promoter region of RASSF1A were detected in 56 (45.2%), 23 (18.6%) and 45 (36.2%) of 124 ESCC samples, respectively. Unmethylation of the promoter region of RASSF1A was detected in 119 (96%) of the 124 corresponding noncancerous tissues. Five (4.0%) of 124 noncancerous tissues showed partial methylation. The presence of hypermethylation was statistically associated with loss of RASSF1A mRNA expression in primary ESCC (p <0.05). There were statistically significant correlations between the presence of hypermethylation and regional lymph node involvement (p=0.000), histological differentiation (p=0.009) and tumor stage (p=0.000).
  
  
  CONCLUSIONS
  Our results suggest that RASSF1A may be one of the ESCC-related TSGs located at 3p21, and hypermethylation of the CpG island promoter of the RASSF1A is associated with the progression of ESCC.
authors: Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, PR China.
authors: Wei-min
authors: WM
authors: Mao
authors: Pei
authors: P
authors: Li
authors: Qiu-qing
authors: QQ
authors: Zheng
authors: Chang-chun
authors: CC
authors: Wang
authors: Ming-hua
authors: MH
authors: Ge
authors: Fu-jun
authors: FJ
authors: Hu
authors: Xian-hua
authors: XH
authors: Fang
authors: Zi-min
authors: ZM
authors: Dong
authors: Zhi-qiang
authors: ZQ
authors: Ling
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins