Studies On The Methylation Of DAZAP2 Promoter And Its Down-regulation In Multiple Myeloma

Tumorigenesis is a multistep,multistage process involving multiple genes.In order to find new multiple myeloma associated genes, Yi-Wu Shi,et al analyzed differential screening of cDNA chips between mRNA from bone marrow mononuclear cells of MM patients and normal controls, and found that DAZAP2(deleted in azoospermia associated protein 2) was the most profoundly down-regulated gene. These results are consistent with that one by detecting expression of DAZAP2 in the bone marrow mononuclear cells of MM patients and normal controls by means of semi-quantitative RT-PCR and Western blot. All these results showed that DAZAP2 expression is down-regulate in multiple myeloma. DAZAP2 may play an important role in the origin and development of MM.Epigenetic changes, such as aberrant DNA methylation, paly important roles in tumorigenesis.DNA methylation can regulate genetic information. Aberrant promoter methylation contributes to tumorigenesis through inducing transcriptional suppression and inactivating tumor suppressors.In order to find the epigenetic mechanism of down-regulation of DAZAP2 in multiple myeloma, we investigated the role of hypermethylation in DAZAP2 gene silencing in KM3 and ARH-77 mutiple myeloma cell lines by methylation-specific PCR(MSP) and compared its methylation status with DAZAP2 mRNA expression.The expression of DAZAP2 was restored in KM3 cell line after 5-aza-2'-deoxycytidine (5-aza-dc) treatment,which DAZAP2 down-regulated. Furthermore,the methylation status of DAZAP2 promoter region and its expression was analyzed in 13 multiple myeloma bone marrow samples and 12 normal bone marrow samples.The results showed that a statistically significantly negative correlation between methylation status of DAZAP2 promoter and DAZAP2 expression down-regulation in multiple myeloma. Thus indicated that hypermethylation may play an important role in down-regulation of DAZAP2 gene expression in multiple myeloma.