title: Downregulation of DLC-1 gene by promoter methylation during primary colorectal cancer progression.
abstract: OBJECTIVE
  DLC-1 is a tumor suppressor gene frequently silenced in human cancers. However, the pathogenicity of DLC-1 epigenetic silencing in the mucosa-adenoma-carcinoma transformation process of colorectal cancer (CRC) has not been studied.
  
  
  METHODS
  Promoter methylation status of DLC-1 was evaluated in 4 human CRC cell lines, 48 normal mucosa, 57 adenomas, and 80 CRC tissues with methylation-sensitive high-resolution melting analysis (MS-HRMA), while the mRNA expression was examined by qPCR. HRMA was utilized to detect the KRAS codon 12, 13 and BRAF V600E mutations.
  
  
  RESULTS
  Partial (1%-10%) and extensive (10%-100%) DLC-1 promoter methylations were observed in 10% and 0% of normal mucosa, 46% and 14% of adenomas, and 60% and 36% of CRCs, respectively. The promoter methylation of DLC-1 was related with the reduction of gene expression and the advanced Duke's stages (Stage C and D). DLC-1 promoter methylation and KRAS mutations are common concurrent pathological alternations.
  
  
  CONCLUSIONS
  Epigenetic alternation plays a key role in the transcriptional silencing of DLC-1. It is also an independent risk factor related to the carcinogenesis of colorectal tumors and spans over its pathogenesis process. Therefore, DLC-1 promoter methylation quantitation may have a promising significance in the evaluation and management of CRC patients.
authors.affiliation: Department of Gastroenterology, Shanghai Changning District Cental Hospital, Shanghai 200336, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Peng
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wu
authors.forename: Yimin
authors.initials: Y
authors.lastname: Chu
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Kuai
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Kang
authors.forename: Xinju
authors.initials: X
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D044127:Epigenesis, Genetic; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D025521:Tumor Suppressor Proteins