Rapid Capture Next-Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B-Cell Precursor ALL
Conflict of interest: Nothing to declare.
Authors’ contribution: U. z. S. planned the study and analyzed data, M. Ad. prepared samples for NGS and analyzed data; G. E. provided patient data and treated patients; D. I. performed NGS and M.Al. performed bioinformatics analyses; M. A. H. planned, conceived, and supervised the study; and U. z. S. and M. A. H. wrote the manuscript. All authors revised and approved the final version of the manuscript.
Abstract
Comprehensive next-generation sequencing (NGS) applications have recently identified various recurrent kinase and cytokine receptor rearrangements in Ph-like B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) amenable to tyrosin kinase inhibitor treatment. For rapid diagnostics of kinase pathway aberrations in minimal residual disease (MRD) high-risk BCP-ALL, we developed a PCR-independent NGS custom enrichment capture panel targeting recurrent genomic alterations, which allows for the identification of unknown 5′ fusion partner genes and precise mapping of variable genomic breakpoints. Using a standardized bioinformatics algorithm, we identified kinase and cytokine receptor rearrangements in the majority of ALL patients with high burden of postinduction MRD and enrichment of IKZF1 mutation or deletion (IKZF1del).
