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. 2024 Apr 13;17(1):84.
doi: 10.1186/s12920-024-01866-y.

Mutation landscape in Chinese nodal diffuse large B-cell lymphoma by targeted next generation sequencing and their relationship with clinicopathological characteristics

Bing Cao  1   2   3   4 , Chenbo Sun  1   2   3 , Rui Bi  1   2   3 , Zebing Liu  1   2   3   5 , Yijun Jia  1   2   3 , Wenli Cui  1   2   3   6 , Menghong Sun  1   2   3 , Baohua Yu  1   2   3 , Xiaoqiu Li  1   2   3 , Xiaoyan Zhou  7   8   9
Affiliations

Mutation landscape in Chinese nodal diffuse large B-cell lymphoma by targeted next generation sequencing and their relationship with clinicopathological characteristics

Bing Cao et al. BMC Med Genomics. .

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL), an aggressive and heterogenic malignant entity, is still a challenging clinical problem, since around one-third of patients are not cured with primary treatment. Next-generation sequencing (NGS) technologies have revealed common genetic mutations in DLBCL. We devised an NGS multi-gene panel to discover genetic features of Chinese nodal DLBCL patients and provide reference information for panel-based NGS detection in clinical laboratories.

Methods: A panel of 116 DLBCL genes was designed based on the literature and related databases. We analyzed 96 Chinese nodal DLBCL biopsy specimens through targeted sequencing.

Results: The most frequently mutated genes were KMT2D (30%), PIM1 (26%), SOCS1 (24%), MYD88 (21%), BTG1 (20%), HIST1H1E (18%), CD79B (18%), SPEN (17%), and KMT2C (16%). SPEN (17%) and DDX3X (6%) mutations were highly prevalent in our study than in Western studies. Thirty-three patients (34%) were assigned as genetic classification by the LymphGen algorithm, including 12 cases MCD, five BN2, seven EZB, seven ST2, and two EZB/ST2 complex. MYD88 L265P mutation, TP53 and BCL2 pathogenic mutations were unfavorable prognostic biomarkers in DLBCL.

Conclusions: This study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations.

Keywords: Diffuse large B-cell lymphoma; Genetic subtype; Mutation; Next-generation sequencing; Targeted sequencing.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
OncoPrint of non-silent mutations for the top genes in 96 Chinese DLBCL patients. Genes affected by non-silent mutations in at least 5 DLBCL samples (5% of cases) are listed. These mutations were annotated by OncoKB in cBioPortal on February 3, 2022. Each row represents a gene, and each column represents a DLBCL sample. Orange squares: inframe mutation (unknown significance); dark green squares: missense mutation (putative driver); light green squares: missense mutation (unknown significance); black squares: truncating mutation (putative driver); blue gray squares: truncating mutation (unknown significance); gray bars: no alterations. Nonsense, frameshift and splice site mutations are referred to as truncating mutations in the figure
Fig. 2
Fig. 2
Schematic diagrams summarizing the mutations identified in SPEN (a) and DDX3X (b). The schematic diagrams were performed with the aid of MutationMapper in cBioPortal. Green circles: missense mutation; black circles: truncating mutation. Nonsense, frameshift and splice site mutations are referred to as truncating mutations in the figure
Fig. 3
Fig. 3
Genetic subtypes of DLBCL. a Prevalence of genetic subtypes of DLBCL classified by the LymphGen tool. b Prevalence of genetic subtypes in COO (Hans) subgroups
Fig. 4
Fig. 4
Kaplan–Meier curves for progression-free survival and overall survival of patients with DLBCL. a Survival analysis was performed on total patients according to BCL2 mutation status. b Survival analysis was performed on patients treated with R-CHOP according to the presence or absence of MYD88 L265P mutation
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