文章：

弥漫性大B细胞淋巴瘤的遗传和表观遗传决定因素

Genetic and epigenetic determinants of diffuse large B-cell lymphoma

原文发布日期：2020-12-04

DOI: 10.1038/s41408-020-00389-w

类型: Review Article

开放获取: 是

英文摘要：

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and is notorious for its heterogeneity, aggressive nature, and the frequent development of resistance and/or relapse after treatment with standard chemotherapy. To address these problems, a strong emphasis has been placed on researching the molecular origins and mechanisms of DLBCL to develop effective treatments. One of the major insights produced by such research is that DLBCL almost always stems from genetic damage that occurs during the germinal center (GC) reaction, which is required for the production of high-affinity antibodies. Indeed, there is significant overlap between the mechanisms that govern the GC reaction and those that drive the progression of DLBCL. A second important insight is that some of the most frequent genetic mutations that occur in DLBCL are those related to chromatin and epigenetics, especially those related to proteins that “write” histone post-translational modifications (PTMs). Mutation or deletion of these epigenetic writers often renders cells unable to epigenetically “switch on” critical gene sets that are required to exit the GC reaction, differentiate, repair DNA, and other essential cellular functions. Failure to activate these genes locks cells into a genotoxic state that is conducive to oncogenesis and/or relapse.
 

摘要翻译： 

弥漫大B-cell淋巴瘤（DLBCL）是最常见的淋巴瘤类型，以其异质性、侵袭性以及在标准化疗后常产生耐药和/或复发而著称。为解决这些问题，研究重点聚焦于探索DLBCL的分子起源与作用机制，以开发有效治疗方案。此类研究获得的重要发现之一是：DLBCL几乎总是源于生发中心（GC）反应过程中发生的基因损伤——该反应是产生高亲和力抗体的必要条件。事实上，调控GC反应的机制与驱动DLBCL进展的机制存在显著重叠。第二个重要发现是：DLBCL中最常见的基因突变涉及染色质和表观遗传学，特别是那些与“书写”组蛋白翻译后修饰（PTMs）的蛋白质相关的突变。这些表观遗传书写蛋白的突变或缺失，常常导致细胞无法通过表观遗传方式“启动”关键基因集——这些基因是细胞退出生发中心反应、完成分化、修复DNA及执行其他重要细胞功能所必需的。若无法激活这些基因，细胞将陷入基因毒性状态，这种状态极易诱发肿瘤形成和/或疾病复发。

原文链接：

Genetic and epigenetic determinants of diffuse large B-cell lymphoma