Methylation contributes to imbalance of PRDM1α/PRDM1bβ expression in diffuse large B-cell lymphoma.

The positive regulatory domain 1 (PRDM1) exists as two isoforms: PRDM1α and PRDM1β. The former is frequently inactivated, while the latter is overexpressed in a subset of diffuse large B-cell lymphoma (DLBCL). To investigate the possible epigenetic alteration ofPRDM1αandPRDM1βexpression, the methylation of these two promoter isoforms was assessed in B lymphoma cell lines and DLBCL samples. Hypomethylation ofPRDM1βCpG islands was preferentially detected in lymphoma cells. However, both high and low methylation ofPRDM1αCpG islands was simultaneously observed in cases of DLBCL compared with the moderate methylation of non-tumor cases. CpG 16–21-specific high methylation was correlated with low expression ofPRDM1αinPRDM1β-positive DLBCL samples. Three increased and one decreased miRNAs were significantly different between cases of DLBCL and non-tumor reactive hyperplasia. Thus, our results indicate that aberrant methylation silencing ofPRDM1αand hypomethylation activation ofPRDM1βare frequent events in DLBCL. [ABSTRACT FROM PUBLISHER]