目的：采用二代测序技术检测结外NK/T细胞淋巴瘤（extranodal natural killer/T-cell lymphoma，ENKTL）目的基因突 变情况，分析其与疾病预后和临床特征的关系， 为ENKTL发病机制、临床诊断和靶向治疗提供依据。方法：根据以往文献报道 筛选其突变会影响淋巴瘤发生发展的基因作为本研究的目的基因。选择2010年8月至2018年10月期间在河北医科大学第四医 院初治的ENKTL患者29例，通过二代测序技术检测组织标本中目的基因突变情况。应用SPSS21.0统计软件分析临床特征、 疾 病预后和目的基因突变情况三者间的关系。结果：筛选得到9个目的基因，其中AT丰富结合域1A基因（AT-rich interactivedomain 1A，ARID1A）为突变率最高的基因，占 34.48%（10 例），其次为赖氨酸甲基转移酶 2D（lysine methyltransferase 2D， KMT2D）（31.03%）、肿瘤蛋白P53（tumor protein P53，TP53）（24.13%）。Kaplan-Meier生存分析显示，KMT2D野生型患者总生存 优于伴有KMT2D基因突变型患者（P=0.006）。KMT2D基因突变情况与ENKTL患者临床资料分析发现，KMT2D基因突变型与 患者临床分期、CRP、白蛋白、淋巴细胞计数、Ki67水平密切相关，具有统计学意义（P<0.05）。通过COX回归多因素分析得出： KMT2D基因突变型为独立预后不良因素（P<0.05）。结论：KMT2D基因在ENKTL中高频突变，并与其预后相关，提示KMT2D 基因在ENKTL发生发展中起重要作用，可作为ENKTL临床治疗潜在的靶点。

Objective: To analyze the mutation of target genes in extranodal natural killer/T-cell lymphoma (ENKTL) by using nextgeneration sequencing, and to explore its relationship with prognosis and clinical characteristics, as to provide evidence for the pathogenesis, clinical diagnosis and targeted therapy of ENKTL. Methods: According to previous literature reports, the genes whose mutations can affect the development of lymphoma were selected as the target genes for this study. 29 patients with ENKTL, who were newly diagnosed at the Fourth Hospital of Hebei Medical University from August 2010 to October 2018, were selected for this study. The mutation of 9 target genes in the specimen was detected by thenext-generationsequencingtechnology.Therelationshipsamongclinicalfeatures,diseaseprognosisandmutationofthetargetgeneswereanalyzedbySPSS21.0statisticalsoftware.Results： ：Ninetargetgenes were were screened. AT-rich interactive-domain 1A(ARID1A) gene showed the highest mutation rate in ENKTL (10 cases, 34.48%) followedbylysinemethyltransferase2D(KMT2D)gene(31.03%)andtumorprotein P53 (TP53) gene (24.13%). Kaplan-Meier survival analysis showed that the overall survival of ENKTL patients with KMT2D gene wild type was significantly better than patients with KMT2D gene mutation (P=0.006). The KMT2D gene mutation was found to besignificantlyrelatedtoclinicalstage,CRP,albumin,lymphocyte count and Ki67 expression in ENKTL patients (all P<0.05). COX regression analysis showed that KMT2D gene mutation was an independent adverse prognostic factor (P<0.05). Conclusion: The KMT2D gene has a high mutant frequency in ENKTL and is associated with patients’prognosis, suggesting that KMT2D gene plays an important role in the initiation and development of ENKTL. It could be used as a clinical therapeutic target for ENKTL.

河北省科技计划资助项目（No. 13277780D）