Loss of promoter methylation contributes to the expression of functionally impaired PRDM1β isoform in diffuse large B-cell lymphoma.
The positive regulatory domain I (PRDM1) is a transcriptional repressor that plays an important role in the B-cell differentiation. PRDM1β 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 PRDM1β expression, methylation of PRDM1β 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. PRDM1β expression corresponded to promoter methylation status. CpG island of PRDM1β promoter possessed significant transcriptional activity, which could be modified by methylation. Loss of promoter methylation of PRDM1β 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.
Zhang
Yi-Wen
YW
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Xie
Hong-Qiang
HQ
Chen
Yu
Y
Jiao
Bo
B
Shen
Zhi-Xiang
ZX
Chen
Sai-Juan
SJ
Zhao
Wei-Li
WL
D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D057890:Epigenomics; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*
D020033:Protein Isoforms; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1