KMT2D基因突变及其共突变基因在弥漫性大B细胞淋巴瘤患者预后中的意义  

Prognostic Significance of KMT2D Gene Mutation and Its Co-mutated Genes in Patients with Diffuse Large B-Cell Lymphoma

作　　者：木提拜尔·米吉提 漆小龙 热那古力·阿不来提 田文昕 刘沙 马卫媛 王增胜[1] 安利[1] 毛敏[1] 木合拜尔·阿布都尔[1] 李燕[1] Mutibaier·MIJITI;QI Xiaolong;Renaguli·ABULAITI;TIAN Wenxin;LIU Sha;MA Weiyuan;WANG Zengsheng;AN Li;MAO Min;Muhebaier·ABUDUER;LI Yan(Department of Hematology,People’s Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院血液科,乌鲁木齐830001

出　　处：《肿瘤防治研究》2025年第2期127-132,共6页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金(82360040)。

摘　　要：目的探讨伴KMT2D基因突变弥漫性大B细胞淋巴瘤(DLBCL)患者的临床特征及其伴随突变基因对预后的影响。方法选择155例初诊DLBCL患者资料,采用二代测序方法检测包括KMT2D突变在内的475种热点基因。根据有无KMT2D基因突变将患者分为KMT2D基因突变型组及KMT2D基因野生型组,比较两组患者临床特征及伴随突变基因的差异和生存差异。结果KMT2D突变频率为31%,突变型患者以老年居多(P=0.07),双表达阳性患者较少(P=0.07)。与KMT2D基因野生型相比,KMT2D基因突变分别与CDKN2A(OR=2.82,P=0.01)和BCL2(OR=3.84,P=0.016)基因共突变率高,而与MYC(OR=0.11,P=0.013)基因突变为相互排斥。单因素生存分析显示突变型组和野生型组总生存(OS)差异无统计学意义(P=0.54),KMT2DmutBTG2mut突变患者较KMT2Dwt BTG2mut(P=0.07)、KMT2Dwt BTG2wt(P=0.05)患者具有较差的OS,而KMT-2Dmut CD79Bmut患者较KMT2Dmut CD79Bwt患者具有较好的OS趋势(P=0.09),未发现其他伴随基因对预后影响。多因素Cox回归分析结果显示,Ann Arbor分期为Ⅲ、Ⅳ期(HR=2.751,95%CI:1.169-6.472,P=0.02)、LDH水平升高(HR=2.461,95%CI:1.396-4.337,P=0.002)、Ki-67指数>80%(HR=1.875,95%CI:1.066-3.299,P=0.029)及KMT-2DmutBTG2mut(HR=4.566,95%CI:1.348-15.471,P=0.015)是DLBCL患者OS的独立危险因素(P<0.05)。结论KMT2D突变的DLBCL患者常伴随多种基因突变,其中伴BTG2基因突变患者预后较差。Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma(DLBCL)accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis.Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained.The second-generation sequencing method was used to detect 475 hotspot genes,including KMT2D mutation.Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation.Clinical characteristics,differences in co-mutated genes,and survival differences between the two groups were compared.Results The frequency of KMT2D mutation was 31%,which is predominantly observed in elderly patients(P=0.07)and less in the double-expressor phenotype(P=0.07).Compared with the KMT2D wild-type group,KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A(OR=2.82,P=0.01)and BCL2(OR=3.84,P=0.016),while being mutually exclusive with MYC gene mutation(OR=0.11,P=0.013).In univariate survival analysis,no statistically significant difference in overall survival(OS)was found between the KMT2D mutation group and the wild-type group(P=0.54).Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut(P=0.07)and KMT2Dwt BTG2wt(P=0.05).On the contrary,patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt(P=0.09),with no prognostic impact observed for other co-mutated genes.Multivariate Cox regression analysis revealed that Ann Arbor stagesⅢandⅣ(HR=2.751,95%CI:1.169-6.472,P=0.02),elevated LDH levels(HR=2.461,95%CI:1.396-4.337,P=0.002),Ki-67 index>80%(HR=1.875,95%CI:1.066-3.299,P=0.029),and KMT2DmutBTG2mut(HR=4.566,95%CI:1.348-15.471,P=0.015)were independent risk factors for OS in patients with DLBCL(P<0.05).Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations,among which patients with a co-mutated BTG2 gene have poor prognosis.

关 键 词：弥漫性大B细胞淋巴瘤 二代测序 KMT2D基因 共突变 预后 

分 类 号：R739.41[医药卫生—肿瘤]