Next Generation Sequencing in routine diagnostics of mature non‐Hodgkin’s lymphomas. A single‐center real‐life data study

Introduction: Precision medicine requires equivalently precise diagnostic methods. The lymphoma diagnoses are primarily based on characteristic patterns of morphology and protein expression detected by immunohistochemistry (IHC). However, integral molecular characterization of lymphomas in clinical diagnostics may improve subclassification and risk-stratification. To accommodate this growing need we implemented a next generation sequencing (NGS) analysis as part of routine diagnostic work up of all mature non-Hodgkin lymphoma (NHL). We present data of mutational profiles with potential complementary diagnostic, prognostic and predictive value detected in our consecutive non-selected cohort of NHL patients. Methods: NGS results from 320 individual consecutive non-selected diagnostic patient samples with a mature NHL were included as a single center study. Patients with both newly diagnosed and relapsed/refractory or progressive disease were included. Diagnoses were according to WHO (4.rev edition). NGS was performed as routine analysis together with standard diagnostic work-up using a custom-made amplicon PCR-based multiplex NGS-panel covering all coding exons and consensus splice sites in 59 genes. Results: Patients are presented in Table 1. Mutations were detected in 93% of the 320 samples. Most B-cell lymphomas (BCL) could be classified definitively and had characteristic mutational profiles as shown in Figure 1, but 24 cases were classified as small cell B-cell lymphomas without defining characteristics (SBCL-NOS). 50% (12/24 cases) of SBCL-NOS could retrospectively be assigned a likely diagnostic subtype according to mutational findings. (1 FL, 6 MZL, 3 LPL and 2 Small lymphocytic lymphoma). Conclusion: Implementation of NGS in routine diagnostics of mature B-cell NHL added diagnostic value to 50% of unclassified cases and provided in a total of 93% of all cases possible biomarkers for disease monitoring as well as potential diagnostic, prognostic and predictive markers for future studies. The research was funded by: Department of Pathology, Herlev-Gentofte Hospital, Denmark Keywords: Diagnostic and Prognostic Biomarkers, Pathology and Classification of Lymphomas No conflicts of interests pertinent to the abstract.