title: Both gene deletion and promoter hyper-methylation contribute to the down-regulation of ZAC/PLAGL1 gene in gastric adenocarcinomas: a case control study.
abstract: OBJECTIVE
  Pleiomorphic adenoma gene-like 1 (PLAGL1, also known as LOT1 and ZAC) is a zinc-finger nuclear transcription factor, which possesses antiproliferative effects and is frequently epigenetically silenced during tumorigenesis. PLAGL1 gene is located on 6q24-25, a chromosomal region that is frequently deleted in various kinds of cancers. Both promoter hyper-methylation and loss of heterozygosity may lead to the down-regulation of PLAGL1 in human somatic cancers. Here we aimed to investigate the abnormalities of PLAGL1 in gastric cancers.
  
  
  METHODS
  We collected 153 case-matched gastric adenocarcinoma (GAC) cases. Quantitative real-time PCR method was applied to evaluate the expression levels as well as gene copy numbers of PLAGL1 in the collected samples. Methylation-specific PCR (MSP) assay was performed to analyze the methylation status of PLAGL1 P1 promoter.
  
  
  RESULTS
  Decreased expression of PLAGL1 mRNA was observed in GAC tissues, especially in advanced GACs. Copy number decrease of PLAGL1 gene in GACs was observed in 9.15% (19 out of 153) of the GAC samples and was closely correlated with gene expression. Methylation status of PLAGL1 promoter in GAC tissues was higher than in normal controls, which was inversely correlated with the expression levels of PLAGL1 mRNA.
  
  
  CONCLUSIONS
  DNA deletion and promoter hyper-methylation both contribute to the down-regulation of PLAGL1 in GACs.
authors.affiliation: Department of Histology & Embryology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Histology & Embryology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Histology & Embryology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Histology & Embryology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Histology & Embryology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Le
authors.affiliation: Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, Guangdong, China.
authors.forename: Luo
authors.initials: L
authors.lastname: Wang
authors.affiliation: Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, Guangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Histology & Embryology, Basic Medical College of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: qxz53@zzu.deu.cn.
authors.forename: Qinxian
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins