Abstract 6560: Identification of distinct patterns in diffuse large B-cell lymphoma through alternative splicing analysis

Abstract Background Aberrant splicing in cancer cells contributes to cellular proliferation, escape from cell death, growth inhibition, invasion and metastasis, and immune escape. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, but the effect of AS on its pathogenesis has not been fully elucidated, so it is essential to find out DLBCL-specific splicing patterns and their potential as treatment targets. Material and Method RNA-Seq dataset from DLBCL patients was retrieved from The Cancer Genome Atlas (TCGA) DLBCL (N=48) and Pan-cancer Analysis of Whole Genomes (PCAWG) DLBC (N=7) were used as the cancer group. In order to identify spliced genes that are significantly different from normal tissue, RNA-Seq data of normal lymphoid tissue produced in two studies of E-MTAB-513 (N=1) and E-MTAB-1733 (N=13) from the BioStudies were downloaded. Sequence reads were aligned to the GRCh38 reference genome using STAR aligner. Results 5,470 genes identified as differentially spliced compared to normal in both rMATS and MAJIQ tools were studied. After sorting the AS events of these genes in order of highest average PSI value, events with an average PSI value of 0.7 or more in the top 2/3 samples and events with an average PSI value of 0.3 or less in the bottom 2/3 samples are selected. 8 exons of 7 genes were involved in Exon skipping (ES) events, 6 exons of 5 genes were involved in mutually exclusive exon (MXE) events, and an exon of a gene was involved in alternative 5' splice site (A5SS) Among these genes, exons 6 and 7 in CD53 showed high PSI values between exons 4 and 9. The average PSI values for exons 6 and 7 of CD53 in DLBCL were 0.923855 and 0.89096, respectively, which were significantly higher than the Normal group (p<0.05). CD53 mediates IL-7R signaling and plays a role in the regulation of normal B-cell development. As a gene coding for cell surface protein, it is involved in various immune systems in T-cell and B-cell surfaces. In healthy tissue, transcripts that skip exon 5 and have a junction between exon 4 and exon 6 or 7 are not yet known and should be further studied. In addition, SLAMF8, which has an exon with a PSI value specific to DLBCL, is also involved lymphocyte activation and regulates B-cell receptor signaling. Conclusion These DLBCL-specific patterns of selective exon usage are expected to be potential targets for cancer immunotherapy. Citation Format: Sanyeowool An, Youngil Koh, Sung-Soo Yoon. Identification of distinct patterns in diffuse large B-cell lymphoma through alternative splicing analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6560.