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

• Published in: BMC medical genomics Vol. 17; no. 1; p. 84
• Main Authors: Cao, Bing, Sun, Chenbo, Bi, Rui, Liu, Zebing, Jia, Yijun, Cui, Wenli, Sun, Menghong, Yu, Baohua, Li, Xiaoqiu, Zhou, Xiaoyan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.04.2024; BioMed Central; BMC
• Subjects: Algorithms; Analysis; Antimitotic agents; Antineoplastic agents; Bcl-2 protein; Biopsy; Cancer; Care and treatment; China; Diagnosis; Diffuse large B-cell lymphoma; DNA sequencing; Dosage and administration; Gene mutations; Genes; Genetic aspects; Genetic subtype; Genomes; Genomics; Health aspects; High-Throughput Nucleotide Sequencing; Humans; Interleukin-1 Receptor-Like 1 Protein; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - genetics; Medical laboratories; Mutation; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Next-generation sequencing; Non-Hodgkin's lymphomas; Nucleotide sequencing; p53 Protein; Patients; Remission (Medicine); Software; Statistical analysis; Targeted sequencing; China; United States > US; Genetic subtype; Next-generation sequencing; Mutation; Targeted sequencing; Diffuse large B-cell lymphoma
• ISSN: 1755-8794; 1755-8794
• DOI: 10.1186/s12920-024-01866-y

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. 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. 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. 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.