State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Int J Hematol. 2010 Oct;92(3):439-44. doi: 10.1007/s12185-010-0689-3. Epub 2010 Sep 22.
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.
PRDM1 阳性调控区 I（PRDM1）是一种转录抑制因子，在 B 细胞分化中发挥重要作用。PRDM1β 异构体在具有侵袭性行为的弥漫性大 B 细胞淋巴瘤的亚群中功能受损且过度表达。为了研究 PRDM1β 表达可能存在的表观遗传改变，通过亚硫酸氢盐测序 PCR 评估了 PRDM1β 启动子的甲基化，并使用 MassARRAY 定量甲基化分析筛选了 DLBCL 患者的肿瘤样本。PRDM1β 表达与启动子甲基化状态相对应。PRDM1β 启动子的 CpG 岛具有显著的转录活性，可被甲基化修饰。与反应性增生相比，淋巴瘤样本中更频繁地检测到 PRDM1β 启动子去甲基化。因此，异常肿瘤抑制基因异构体的去甲基化可能与淋巴瘤的进展有关。
