Abstract
Background:
Primary testicular lymphomas (PTLs) are extra-nodal large B-cell lymphomas (LBCLs) that respond poorly to current empirical treatment options. To date, no PTL whole-exome sequencing analysis based on the Chinese population has been reported. The main objective of this study was to explore the genomic landscape of PTDLBCL, correlating the results with clinical, histological, and immunogenetic features.
Methods:
We retrospectively analyzed the disease characteristics in a series of 20 patients (13 paired data and 7 unpaired data). In all cases, the diagnosis of PTL was made using appropriate diagnostic criteria for the 2008 WHO classification of lymphoid tumors with combinations of histologic, immunohistochemical, flow cytometric, and genetic evaluation. Medical records were reviewed for demographic and clinical data. We performed whole-exome next-generation sequencing (NGS) and mapped the mutational landscape. Based on the differential gene results, we performed KEGG and GO enrichment analysis, and five potential new pathogenic genes for DLBCL were obtained based on the Polyphen score.
Results:
A total of 20 DLBCL samples were collected. All samples were subjected to whole-exome sequencing (WES). A standard bioinformatics analysis process was used to identify somatic mutations in each sample, and an average of 1200 somatic mutations was identified, involving an average of 420 mutated genes. (Figure 1.) More than 85% of the somatic mutations were found in only 1 sample, indicating that somatic mutations are highly heterogeneous. In the matched 13 cases, we validated common gene mutations that have been reported, including PIM1 53.84% (7/13), CD79B 38.46% (5/13), CDKN2A 15.38% (2/13), and MYD88 15.38% (2/13). Venn diagram shows that 25% of the mutated genes were specific to the relapsed sample. GO analysis (Figure 2) shows the functional enrichment and differences between relapsed and non-relapsed samples. Non-relapsed samples are enriched in the herpes simplex virus 1 infection pathway. (Figure 3). Focusing on relapsed/non-relapsed samples, we identified 12 mutated genes specific to relapsed samples. Mutation Polyphen scores were calculated to assess mutation deleteriousness. Five potential new pathogenic genes for DLBCL were obtained.
Conclusions:
Based on whole-sequencing data, we validated the previously reported common genes for PTDLBCL. In addition, we performed GO and KEGG analysis according to the relapsed and non-relapsed groups. In addition, based on the difference in enrichment results, 12 significantly enriched mutated genes in relapsed DLBCL samples are obtained, and mutation Polyphen scores are calculated to assess mutation deleteriousness. And 5 potential new pathogenic genes of DLBCL are identified.
No relevant conflicts of interest to declare.
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