Loss of promoter methylation contributes to the expression of functionally impaired PRDM1beta isoform in diffuse large B-cell lymphoma.

摘要

The positive regulatory domain I (PRDM1) is a transcriptional repressor that plays an important role in the B-cell differentiation. PRDM1beta isoform is functionally impaired and overexpressed in a subset of diffuse large B-cell lymphoma with aggressive behavior. To investigate the possible epigenetic alteration on PRDM1beta expression, methylation of PRDM1beta promoter was assessed in B-lymphoma cell lines by bisulfite-sequencing PCR and screened in tumor samples of DLBCL patients using MassARRAY-quantitative methylation analysis. PRDM1beta expression corresponded to promoter methylation status. CpG island of PRDM1beta promoter possessed significant transcriptional activity, which could be modified by methylation. Loss of promoter methylation of PRDM1beta was more frequently detected in lymphoma samples than in reactive hyperplasia. Thus, demethylation of abnormal tumor suppressor gene isoform might be linked to lymphoma progression.