Li Weijie
Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, USA
(SET Domain Containing 2, Histone Lysine Methyltransferase) is the only human gene encoding the histone methyltransferase responsible for trimethylation of lysine 36 of histone H3. SETD2 protein is involved in multiple important cellular processes that include transcriptional regulation, DNA damage repair, alternative RNA splicing, genomic stability, apoptotic response, and interferon response. As a tumor suppressor, loses its activities by loss-of-function mutations in a wide spectrum of tumors. The alterations of are the most common genetic changes detected in monomorphic epitheliotropic intestinal T-cell lymphoma, seen in over 90% of the cases. is the commonest silenced gene detected in hepatosplenic T-cell lymphoma, seen in 25% of the cases. alterations have been detected in approximately 10% of precursor B-cell lymphoblastic leukemia/lymphoma cases, and commonly gained in the relapse of this disease. alterations have also been found in about 10% of early-T-precursor lymphoblastic leukemia, up to 10% of diffuse large B-cell lymphoma, up to 7% of chronic lymphoblastic leukemia/small lymphocytic lymphoma, and in a small portion of other lymphoid malignancies. Experimental loss of SETD2 can promote tumor cell proliferation and result in chemotherapy resistance. Targeting SETD2 may offer a potential therapeutic strategy for these lymphoid malignancies.
（含SET结构域蛋白2，组蛋白赖氨酸甲基转移酶）是人类唯一编码负责组蛋白H3赖氨酸36三甲基化的组蛋白甲基转移酶的基因。SETD2蛋白参与多种重要的细胞过程，包括转录调控、DNA损伤修复、可变RNA剪接、基因组稳定性、凋亡反应和干扰素反应。作为一种肿瘤抑制因子，在多种肿瘤中因功能丧失性突变而失去其活性。SETD2的改变是在单形上皮嗜性肠道T细胞淋巴瘤中检测到的最常见的基因变化，超过90%的病例中可见。SETD2是在肝脾T细胞淋巴瘤中检测到的最常见的沉默基因，25%的病例中可见。在大约10%的前体B细胞淋巴母细胞白血病/淋巴瘤病例中检测到SETD2改变，并且在该疾病复发时通常获得。在大约10%的早期T前体淋巴母细胞白血病、高达10%的弥漫性大B细胞淋巴瘤、高达7%的慢性淋巴细胞白血病/小淋巴细胞淋巴瘤以及一小部分其他淋巴恶性肿瘤中也发现了SETD2改变。实验性SETD2缺失可促进肿瘤细胞增殖并导致化疗耐药。靶向SETD2可能为这些淋巴恶性肿瘤提供一种潜在的治疗策略。
