title: Rapid Capture Next-Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B-Cell Precursor ALL.
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 (IKZF1(del) ).
authors.affiliation: Center for Diagnostics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Udo Zur
authors.initials: UZ
authors.lastname: Stadt
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.affiliation: Virus Genomics, Heinrich-Pette-Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Indenbirken
authors.affiliation: Virus Genomics, Heinrich-Pette-Institute for Experimental Virology, Hamburg, Germany.|Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Malik
authors.initials: M
authors.lastname: Alawi
authors.affiliation: Center for Diagnostics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Adao
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Research Institute Children's Cancer Center, Hamburg, Germany.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Horstmann
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D008297:Male; D009154:Mutation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*
chemical_list: C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor
keywords: NGS; Ph-like ALL; acute lymphoblastic leukemia; genomic breakpoints