【摘要】 目的：探讨胃肠道弥漫大B细胞淋巴瘤(PGI-DLBCL)患者肿瘤组织中基因突变情况，分析其与临床特征及预后的相关性。方法：收集2009年3月至2021年3月在新疆维吾尔自治区人民医院诊治的初诊PGI-DLBCL患者31例，及同期性别、年龄、民族相匹配的结内DLBCL患者81例，使用475个淋巴瘤相关基因组对患者肿瘤组织进行靶向测序，分析PGI-DLBCL及结内DLBCL患者突变图谱及生物信号转导通路差异，探讨PGI-DLBCL中突变基因与年龄、乳酸脱氢酶水平、Lugano分期、IPI评分、细胞起源分型及患者总生存期(OS)和无进展生存期(PFS)间的关系。结果：在PGI-DLBCL中共检测到50个高频突变基因(基因突变个数≥3个，突变频率≥10%)。与结内DLBCL相比，PGI-DLBCL患者中GNA13、EZH2以及FBXO11基因突变率显著更高。BTG2和CD79B基因突变与IPI评分高危及高龄密切相关，老年患者中更易检测到MYD88基因突变，P2RY8、KMT2D基因突变分别与疾病早期和高乳酸脱氢酶相关。仅在GCB亚型中检测到GNA13基因发生突变，而KMT2C、IRF4、ID3基因在non-GCB亚型中突变更为频繁。进一步研究发现，CARD11、FANCA、ID3基因突变的患者表现出更低的5年OS率(均P<0.05),ID3和NFKBIE基因突变与较差的PFS相关(均P<0.05)，多因素生存分析结果提示ID3基因突变是影响PGIDLBCL患者OS(HR=6.213,95%CI:1.215-31.770,P=0.028)及PFS(HR=0.060,95%CI:0.012-0.307,P=0.001)的独立不良预后因素。结论：PGI-DLBCL具有特征性的基因突变谱，与结内DLBCL发生发展分子机制存在差异。ID3基因突变是预测PGI-DLBCL预后不良的独立预后因子。更多还原

【Abstract】 Objective:To investigate the gene mutations in tumor tissues of patients with primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL),and analyze its relationship with clinical features and prognosis.Methods:A total of 31 newly diagnosed PGI-DLBCL patients treated in the People ’ s Hospital of Xinjiang Uygur Autonomous Region from March 2009 to March 2021 and 81 nodal DLBCL patients matching gender,age,and ethnic group during the same period were collected.The sequencing of patients ’ tumor tissues were targeted by a panel of 475lymphoma-related genes.The differences of mutational profiles and biological signaling pathway between PGI-DLBCL and nodal DLBCL were analyzed.The relationship between mutated genes and age,lactate dehydrogenase(LDH)level,Lugano stage,IPI score,cell origin typing,overall survival(OS) and progression-free survival(PFS) of PGIDLBCL patients were investigated.Results:A total of 50 high frequency mutated genes(number of gene mutations≥3,mutation frequency≥10%) were detected in PGI-DLBCL.The mutation rates of GNA13,EZH2,and FBXO11genes in PGI-DLBCL patients were significantly higher than those in nodal DLBCL patients.BTG2 and CD79B mutations were closely associated with high-risk of IPI scores and the elderly.MYD88 mutations were more easily detected in the elderly patients.And mutations of the P2RY8 and KMT2D gene were related to early stage of the disease and high LDH,respectively.Only GNA13 mutations were detected in GCB subtype,while KMT2C,IRF4 and ID3mutations were most frequent in non-GCB subtype.Further studies found that patients with CARD11,FANCA and ID3mutations showed lower 5-year OS rate(all P <0.05),while ID3 and NFKBIE mutations were associated with poorer PFS(both P <0.05).The results of multivariate survival analysis suggested that ID3 mutation was an independent adverse prognostic factor for OS(HR=6.213,95% CI:1.215-31.770,P=0.028) and PFS(HR=0.060,95% CI:0.012-0.307,P=0.001) in PGI-DLBCL patients.Conclusion:PGI-DLBCL has a characteristic gene mutation spectrum,which is different from the molecular mechanism of nodal DLBCL development.ID3 gene mutation is an independent prognostic factor for predicting poor prognosis of PGI-DLBCL.更多还原