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

Mutibaier·mijiti; Xiaolong QI; Renaguli·abulaiti; Wenxin Tian; Sha Liu; Weiyuan MA; Zengsheng Wang; Li AN; Min Mao; Muhebaier·abuduer; Yan LI

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

VernacularTitle: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
Author: Mutibaier·MIJITI ¹ ; Xiaolong QI ¹ ; Renaguli·ABULAITI ¹ ; Wenxin TIAN ¹ ; Sha LIU ¹ ; Weiyuan MA ¹ ; Zengsheng WANG ¹ ; Li AN ¹ ; Min MAO ¹ ; Muhebaier·ABUDUER ¹ ; Yan LI ¹
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1. Department of Hematology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China.
Publication Type:CLINICALRESEARCH
Keywords: Diffuse large B-cell lymphoma; Next-generation sequencing; KMT2D gene; Co-mutation; Prognosis
From: Cancer Research on Prevention and Treatment 2025;52(2):127-132
CountryChina
Language:Chinese
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.