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.
J Mol Diagn. 2021 Aug;23(8):959-974. doi: 10.1016/j.jmoldx.2021.05.007. Epub 2021 Jun 1.
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.
B 细胞肿瘤是一组具有明显临床异质性的血液系统恶性肿瘤，其基因组结构最近通过下一代测序（NGS）研究得到了证实。由于多种遗传缺陷具有潜在或明确的临床影响，因此人们希望更全面地检测诊断、预后和预测标志物。本研究介绍了一种名为 LYmphoid NeXt-generation sequencing（LYNX）的综合、定制、基于捕获的 NGS 面板的设计、验证和实施，用于分析最常见的淋巴肿瘤（慢性淋巴细胞白血病、急性淋巴细胞白血病、弥漫性大 B 细胞淋巴瘤、滤泡性淋巴瘤和套细胞淋巴瘤）的标准和新型分子标志物。单次 LYNX 检测可提供以下内容：i）准确检测 70 个淋巴瘤相关基因的所有编码外显子和剪接位点的突变，灵敏度为 5%变异等位基因频率，ii）可靠识别至少 20%克隆细胞分数中≥6 Mb 的全基因组和≥300 kb 的反复染色体异常，iii）评估免疫球蛋白和 T 细胞受体基因重排，以及 iv）淋巴瘤特异性易位检测。专门的生物信息学管道被设计用于检测所有上述标志物。LYNX 面板是一种全面、最新的工具，适用于常规检测淋巴肿瘤，具有研究和临床应用价值。它允许在临床实践中广泛采用基于捕获的靶向 NGS，并对淋巴增生性疾病患者进行个性化管理。
