Clinical Validation of a Targeted Next-Generation Sequencing Panel for Lymphoid Malignancies

Abstract

Lymphoid malignancies are a heterogeneous group of hematological disorders characterized by a diverse range of morphological, immunophenotypic and clinical features. Next generation sequencing (NGS) is increasingly being applied to delineate the complex nature of these malignancies and identify high value biomarkers with diagnostic, prognostic, or therapeutic benefit. However, there are various challenges in using NGS routinely to characterize lymphoid malignancies including pre-analytic issues such as sequencing DNA from formalin-fixed paraffin-embedded tissue and optimizing the bioinformatic workflow for accurate variant calling and filtering. This study reports the clinical validation of a custom capture-based NGS panel to test for molecular markers in a range of lymphoproliferative diseases and histiocytic neoplasms. The fully validated clinical assay represents an accurate and sensitive tool for detection of single nucleotide variants (SNV) and small insertion/deletion events (INDEL) to facilitate the characterization and management of patients with hematologic cancers specifically of lymphoid origin.