THERAPEUTIC IMPLICATIONS OF TARGETED SEQUENCING AND miRNA-SEQ OF B CELL LYMPHOMAS

Next-generation sequencing (NGS)-based approaches facilitated the identification of genomic and transcriptomic alterations associated withthe development of B-cell lymphomas. Identification of these aberrancies during diagnosis may be helpful in choosing the most appropriate targetedtherapy. Follicular lymphoma and Burkitt lymphoma are B-cell non-Hodgkin lymphomas with the potential to benefit from molecular targeted therapy. Targeted sequencing or miRNA-Seq were performed on FFPE tumor tissues of FL and pediatric BL (pBL) cases, respectively, usingthe HiSeq system. Cancer- associated somatic mutations were identified in FL tumor tissue DNA samples through a computational bioinformatics pipeline.miRNAs overexpressed in pBL cases compared with the tonsil centroblasts of non-cancer control cases were identified through differential expressionanalyses. Sanger sequencing or qRT-PCR were used to cross-validate targeted NGS and miRNA-Seq results, respectively. The literature search wasperformed to evaluate the therapeutic potential of these somatic mutations and upregulated miRNAs. Targeted sequencing of FL tumor tissues revealed activating mutations in genes of biological processes or oncogenic signaling pathways. SeveralmiRNAs were identified to be significantly overexpressed in pBL cases. The literature search revealed that targeted therapeutic approaches may beavailable for the FL or pBL patients with the identified mutations or upregulated miRNAs in tumor tissues. Targeted NGS may be applied during diagnosis to choose appropriate therapy for FL patients. Upregulated miRNAs provide uniqueopportunities for personalized targeted therapy of pBL patients.