The prognostic impact of CDH1 and MEG3 methylation status in multiple myeloma

Epigenetic abnormalities, including DNA methylation, are thought to contribute to the pathobiology of multiple myeloma (MM). Recent studies have shown that the hypermethylation of tumor suppressor gene promoters is associated with MM progression; however, its prognostic significance remains unclear. In this study, we focused on the methylation status of two genes, cadherin-1 (CDH1) and maternally expressed gene 3 (MEG3), and found that methylation was associated with poor prognosis in MM. We determined the methylation status of CDH1 and MEG3 in 57 patients with newly diagnosed MM by methylation-specific polymerase chain reaction using bone marrow (BM) clot samples. The frequencies of promoter hypermethylation for CDH1 and MEG3 were 25% and 21.2%, respectively. We observed that CDH1 promoter hypermethylation may have contributed to unfavorable clinical outcomes such as low hemoglobin levels, high serum creatinine levels, and a high BM plasma cell percentage. We also observed a trend toward reduced overall survival in the CDH1 methylated and MEG3 unmethylated patient groups. This suggested that CDH1 promoter hypermethylation and MEG3 promoter unmethylation status may predict poor MM prognoses. These findings provide new insights into prognostic assessment in MM based on the methylation status of the CDH1 and MEG3 genes.