染色质修饰因子的突变；生发中心B细胞淋巴瘤的一个新特征。
Mutation of chromatin modifiers; an emerging hallmark of germinal center B-cell lymphomas.
作者信息
Lunning M A, Green M R
机构信息
Lymphoma Precision Medicine Laboratory, Dr James O Armitage Center for Leukemia and Lymphoma Research, University of Nebraska Medical Center, Omaha, NE, USA.
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
出版信息
Blood Cancer J. 2015 Oct 16;5(10):e361. doi: 10.1038/bcj.2015.89.
Subtypes of non-Hodgkin's lymphomas align with different stages of B-cell development. Germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt's lymphoma (BL) each share molecular similarities with normal GCB cells. Recent next-generation sequencing studies have gained insight into the genetic etiology of these malignancies and revealed a high frequency of mutations within genes encoding proteins that modifying chromatin. These include activating and inactivating mutations of genes that perform post-translational modification of histones and organize chromatin structure. Here, we discuss the function of histone acetyltransferases (CREBBP, EP300), histone methyltransferases (KDM2C/D, EZH2) and regulators of higher order chromatin structure (HIST1H1C/D/E, ARID1A and SMARCA4) that have been reported to be mutated in ⩾5% of DLBCL, FL or BL. Mutations of these genes are an emerging hallmark of lymphomas with GCB-cell origins, and likely represent the next generation of therapeutic targets for these malignancies.
非霍奇金淋巴瘤的亚型与B细胞发育的不同阶段相对应。生发中心B细胞（GCB）样弥漫性大B细胞淋巴瘤（DLBCL）、滤泡性淋巴瘤（FL）和伯基特淋巴瘤（BL）各自与正常GCB细胞存在分子相似性。最近的下一代测序研究深入了解了这些恶性肿瘤的遗传病因，并揭示了编码修饰染色质蛋白的基因内高频突变。这些包括对组蛋白进行翻译后修饰并组织染色质结构的基因的激活和失活突变。在此，我们讨论据报道在≥5%的DLBCL、FL或BL中发生突变的组蛋白乙酰转移酶（CREBBP、EP300）、组蛋白甲基转移酶（KDM2C/D、EZH2）和高级染色质结构调节因子（HIST1H1C/D/E、ARID1A和SMARCA4）的功能。这些基因的突变是起源于GCB细胞的淋巴瘤的一个新特征，并且可能代表这些恶性肿瘤的下一代治疗靶点。
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