B-cell neoplasms represent a clinically heterogeneous group of hematologic malignancies with considerably diverse genomic architecture recently endorsed by next-generation sequencing (NGS) studies. Because multiple genetic defects have a potential or confirmed clinical impact, a tendency toward more comprehensive testing of diagnostic, prognostic, and predictive markers is desired. This study introduces the design, validation, and implementation of an integrative, custom-designed, capture-based NGS panel titled LYmphoid NeXt-generation sequencing (LYNX) for the analysis of standard and novel molecular markers in the most common lymphoid neoplasms (chronic lymphocytic leukemia, acute lymphoblastic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma). A single LYNX test provides the following: i) accurate detection of mutations in all coding exons and splice sites of 70 lymphoma-related genes with a sensitivity of 5% variant allele frequency, ii) reliable identification of large genome-wide (≥6 Mb) and recurrent chromosomal aberrations (≥300 kb) in at least 20% of the clonal cell fraction, iii) the assessment of immunoglobulin and T-cell receptor gene rearrangements, and iv) lymphoma-specific translocation detection. Dedicated bioinformatic pipelines were designed to detect all markers mentioned above. The LYNX panel represents a comprehensive, up-to-date tool suitable for routine testing of lymphoid neoplasms with research and clinical applicability. It allows a wide adoption of capture-based targeted NGS in clinical practice and personalized management of patients with lymphoproliferative diseases.

Center of Molecular Medicine Central European Institute of Technology Masaryk University Brno Czech Republic

Center of Molecular Medicine Central European Institute of Technology Masaryk University Brno Czech Republic; Department of Internal Medicine 2 Hematology and Oncology University Medical Center Schleswig Holstein Kiel Germany

Department of Internal Medicine Hematology and Oncology Masaryk University and University Hospital Brno Brno Czech Republic

Department of Internal Medicine Hematology and Oncology Masaryk University and University Hospital Brno Brno Czech Republic; Center of Molecular Medicine Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Internal Medicine Hematology and Oncology Masaryk University and University Hospital Brno Brno Czech Republic; Center of Molecular Medicine Central European Institute of Technology Masaryk University Brno Czech Republic; Institute of Medical Genetics and Genomics Faculty of Medicine Masaryk University and University Hospital Brno Brno Czech Republic

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