Bohers Elodie, Mareschal Sylvain, Bertrand Philippe, Viailly Pierre Julien, Dubois Sydney, Maingonnat Catherine, Ruminy Philippe, Tilly Hervé, Jardin Fabrice
INSERM U918, Centre Henri Becquerel, Rouen University and IRIB , Rouen , France.
Leuk Lymphoma. 2015 May;56(5):1213-22. doi: 10.3109/10428194.2014.941836. Epub 2014 Oct 9.
Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma, accounting for 30-40% of newly diagnosed non-Hodgkin lymphomas. Historically, DLBCL has been thought to involve recurrent translocations of the immunoglobulin heavy (IGH) locus and the deregulation of rearranged oncogenes. Whole exome sequencing (WES) of more than 200 DLBCLs has completely redefined the genetic landscape of the disease by identifying recurrent single nucleotide variants and providing new therapeutic opportunities in DLBCL molecular subtypes. Some of these somatic mutations target genes that play a crucial role in B-cell function (B cell receptor [BCR] signaling, nuclear factor κB [NF-κB] pathway, Toll-like receptor [TLR] signaling and phosphatidylinositol 3-kinase [PI3K] pathway), immunity, cell cycle/apoptosis or chromatin modification. In this review, following an overview of the somatic mutations reported in DLBCL, we focus on activating and clustered mutations targeting genes including MYD88, CD79A/B, EZH2 and CARD11 and discuss their clinical and therapeutic relevance in the precision medicine era.
弥漫性大B细胞淋巴瘤（DLBCL）是淋巴瘤最常见的形式，占新诊断非霍奇金淋巴瘤的30%-40%。从历史上看，DLBCL被认为涉及免疫球蛋白重链（IGH）基因座的反复易位以及重排癌基因的失调。对200多个DLBCL进行全外显子测序（WES），通过识别反复出现的单核苷酸变异并为DLBCL分子亚型提供新的治疗机会，彻底重新定义了该疾病的遗传格局。其中一些体细胞突变靶向在B细胞功能（B细胞受体[BCR]信号传导、核因子κB[NF-κB]途径、Toll样受体[TLR]信号传导和磷脂酰肌醇3激酶[PI3K]途径）、免疫、细胞周期/凋亡或染色质修饰中起关键作用的基因。在本综述中，在概述DLBCL中报道的体细胞突变后，我们重点关注靶向包括MYD88、CD79A/B、EZH2和CARD11等基因的激活突变和聚集突变，并讨论它们在精准医学时代的临床和治疗相关性。
