<i>KMT2D</i>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

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; 安利; 毛敏; 木合拜尔·阿布都尔; 李燕

doi:10.3971/j.issn.1000-8578.2025.24.0557

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

摘要

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），KMT2D^mutBTG2^mut突变患者较KMT2D^wt BTG2^mut（P=0.07）、KMT2D^wt BTG2^wt（P=0.05）患者具有较差的OS，而 KMT2D^mut CD79B^mut 患者较KMT2D^mut CD79B^wt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KMT2D^mutBTG2^mut（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。

Abstract:
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 KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (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 KMT2D^mutBTG2^mut(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.

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