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Pediatr Blood Cancer. 2016 Jul;63(7):1283-6. doi: 10.1002/pbc.25975. Epub 2016 Mar 23.

Rapid Capture Next-Generation Sequencing in Clinical Diagnostics of Kinase Pathway Aberrations in B-Cell Precursor ALL.

Author information

1
Center for Diagnostics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
2
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3
Virus Genomics, Heinrich-Pette-Institute for Experimental Virology, Hamburg, Germany.
4
Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
5
Research Institute Children's Cancer Center, Hamburg, Germany.

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) ).

KEYWORDS:

NGS; Ph-like ALL; acute lymphoblastic leukemia; genomic breakpoints

PMID:
27007619
DOI:
10.1002/pbc.25975
[Indexed for MEDLINE]

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