Molecular diagnostics and reporting in lymphoid malignancies: Current status and beyond

Abstract

Thanks to the advent of next‐generation sequencing (NGS) technologies more than 10 years ago, the genomic landscape of most larger cancer types has been unraveled. Hematological and lymphoid malignancies were among the first cancer types to be sequenced, probably as they are more easily accessible. Based on these studies, the number of clinically relevant genetic aberrations with diagnostic, prognostic, and/or predictive impact has increased rapidly. This increases demands on molecular diagnostics to ensure that different types of genetic alterations can be readily detected in a diagnostic setting and within a reasonable time frame. For hematological malignancies, genetics have been an integral part of diagnostics since decades, including methods such as cytogenetics, fluorescence in situ hybridization (FISH) and targeted mutational analysis, and/or Sanger sequencing (Figure 1). With the more powerful NGS technologies, targeted gene panels have been added to the arsenal of methods in the diagnostic laboratory. Regardless of the type of diagnostic test, it is essential to harmonize methodology according to international standards and guidelines. To ensure comparable results, especially in multicenter studies, it is equally important that the interpretation of the results and the clinical reporting follow established guidelines. This is particularly relevant as genetic test results are becoming more complex with different NGS assays covering a range of different genetic aberrations. This paper gives an overview of different state‐of‐the‐art molecular technologies that are applied in clinical diagnostics of lymphoid malignancies, their advantages, and limitations. It also discusses aspects that need to be considered to harmonize clinical interpretation and reporting of NGS data.