title: Methylation of RASSF1A gene promoter and the correlation with DNMT1 expression that may contribute to esophageal squamous cell carcinoma.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma is one of the most common malignancies in the world. Studies have confirmed that there are many genes abnormally hypermethylated in esophageal squamous cell carcinoma. The objective is to detect methylation of the RASSF1A gene promoter and the expression of the DNA methyltransferase 1 (DNMT1) protein in esophageal cancer tissue and discuss their relationship with esophageal squamous cell carcinoma.
  
  
  METHODS
  The CpG island methylation status of RASSF1A genes were analyzed in 100 cases of tumor specimens as well as their adjacent tissues which was used for methylation-specific polymerase chain reaction (MSP). The expression of DNMT1 protein was determined by immunohistochemistry. Difference between measurement data and categorical data was compared through analysis of t test and chi-square test. All the statistics were taken with a bilateral test. The difference was statistically significant (P < 0.05).
  
  
  RESULTS
  The promoter methylation of the RASSF1A gene promoter has been detected in 45 out of 100 (45%) esophageal squamous carcinoma cases, while methylation of RASSF1A gene has been detected in 2 out of 100 adjacent normal tissues (2%). The RASSF1A gene promoter was highly methylated in cancer tissues, and there were significant differences between normal esophagus tissues and esophageal squamous carcinoma (P < 0.05). The expression of DNMT1 protein has been detected in 61 out of 100 (61%) esophageal squamous carcinoma cases, including 41 cases in the above 45 methylated samples of RASSF1A gene promoter, and none in adjacent tissues. DNMT1 proteins are highly expressed in cancer tissues, and there were significant differences (P < 0.05). In positive cases for methylation of RASSF1A, the DNMT1 protein had been detected in 41 out of 45 (91%), while in non-methylated cancer cases, 20 out of 55(36.3%), and the difference is significant (P < 0.05).
  
  
  CONCLUSIONS
  Esophageal squamous carcinoma tumorigenesis may be related with hypermethylation of DNMT1 and RASSF1A promoter CpG island due to their high expression and also their hypermethylation.
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. duzhenzong@sina.com.
authors.forename: Zhenzong
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. 1136845723@qq.com.
authors.forename: Kui
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. sxlshandong@163.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. 277676558@qq.com.
authors.forename: Angui
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. docwanghy@sina.com.
authors.forename: Haiyong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. 281986482@qq.com.
authors.forename: Lifei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. 472556577@qq.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. 1023611447@qq.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, China. guilinsjf@163.com.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human