Both gene deletion and promoter hyper-methylation contribute to the down-regulation of ZAC/PLAGL1 gene in gastric adenocarcinomas: A case control study

Summary Background and 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. Conclusion DNA deletion and promoter hyper-methylation both contribute to the down-regulation of PLAGL1 in GACs.