文章：

肿瘤抑制基因PRDM1/Blimp-1的高甲基化支持其在EBV阳性伯基特淋巴瘤中的致病作用

Hypermethylation of the tumor suppressor gene PRDM1/Blimp-1 supports a pathogenetic role in EBV-positive Burkitt lymphoma

原文发布日期：2014-11-07

DOI: 10.1038/bcj.2014.75

类型: Original Article

开放获取: 是

英文摘要：

PRDM1/Blimp-1 is a tumor suppressor gene in the activated B-cell subtype of diffuse large B-cell lymphomas. Its inactivation contributes to pathogenesis in this setting by impairing terminal B-cell differentiation induced by constitutive nuclear factor-κB activation. The role of PRDM1 in Burkitt lymphoma (BL) lymphomagenesis is not known. Here we identified hypermethylation of the promoter region and exon 1 of PRDM1 in all six Epstein–Barr virus (EBV)-positive BL cell lines and 12 of 23 (52%) primary EBV-positive BL or BL-related cases examined, but in none of the EBV-negative BL cell lines or primary tumors that we assessed, implying a tumor suppressor role for PRDM1 specifically in EBV-associated BL. A direct induction of PRDM1 hypermethylation by EBV is unlikely, as PRDM1 hypermethylation was not observed in EBV-immortalized B lymphoblastoid cell lines. Treatment of EBV-positive BL cells with 5′ azacytidine resulted in PRDM1 induction associated with PRDM1 demethylation, consistent with transcriptional silencing of PRDM1 as a result of DNA methylation. Overexpression of PRDM1 in EBV-positive BL cell lines resulted in cell cycle arrest. Our results expand the spectrum of lymphoid malignancies in which PRDM1 may have a tumor suppressor role and identify an epigenetic event that likely contributes to the pathogenesis of BL.

摘要翻译： 

PRDM1/Blimp-1是弥漫性大B细胞淋巴瘤活化B细胞亚型中的一个肿瘤抑制基因。其功能失活通过损害由持续性核因子κB活化诱导的终末B细胞分化，从而在该背景下促进发病机制。PRDM1在伯基特淋巴瘤（BL）淋巴瘤生成中的作用尚不清楚。在此，我们发现所有六种爱泼斯坦-巴尔病毒（EBV）阳性BL细胞系以及23例（52%）原发性EBV阳性BL或BL相关病例中的12例存在PRDM1启动子区域和外显子1的高甲基化，但在我们评估的EBV阴性BL细胞系或原发性肿瘤中均未发现，这暗示PRDM1在EBV相关BL中特异性发挥肿瘤抑制作用。EBV直接诱导PRDM1高甲基化的可能性不大，因为在EBV永生化的B淋巴母细胞样细胞系中未观察到PRDM1高甲基化。用5'-氮杂胞苷处理EBV阳性BL细胞导致PRDM1去甲基化相关的PRDM1诱导，这与DNA甲基化导致的PRDM1转录沉默一致。在EBV阳性BL细胞系中过表达PRDM1导致细胞周期停滞。我们的研究结果扩展了PRDM1可能具有肿瘤抑制作用的淋巴恶性肿瘤谱系，并确定了一个可能参与BL发病机制的表观遗传事件。

原文链接：

Hypermethylation of the tumor suppressor gene PRDM1/Blimp-1 supports a pathogenetic role in EBV-positive Burkitt lymphoma