Characterization of novel, recurrent genomic rearrangements as sensitive MRD targets in childhood B-cell precursor ALL.

Autor: Zur Stadt U; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg, 20246, Hamburg, Germany. zurstadt@uke.de., Alawi M; Bioinformatics Core Facility, University Medical Center Hamburg, 20246, Hamburg, Germany., Adao M; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg, 20246, Hamburg, Germany., Indenbirken D; Heinrich Pette Institute, Leibniz-Institute for Experimental Virology, 20251, Hamburg, Germany., Escherich G; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg, 20246, Hamburg, Germany., Horstmann MA; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg, 20246, Hamburg, Germany.; Research Institute Children's Cancer Center Hamburg, 20251, Hamburg, Germany.
Jazyk: angličtina
Zdroj: Blood cancer journal [Blood Cancer J] 2019 Nov 29; Vol. 9 (12), pp. 96. Date of Electronic Publication: 2019 Nov 29.
DOI: 10.1038/s41408-019-0257-x
Abstrakt: B-cell precursor (BCP) ALL carry a variety of classical V(D)J rearrangements as well as genomic fusions and translocations. Here, we assessed the value of genomic capture high-throughput sequencing (gc-HTS) in BCP ALL (n = 183) for the identification and implementation of targets for minimal residual disease (MRD) testing. For TRδ, a total of 300 clonal rearrangements were detected in 158 of 183 samples (86%). Beside clonal Vδ2-Dδ3, Dδ2-Dδ3, and Vδ2-Jα we identified a novel group of recurrent Dδ-Jα rearrangements, comprising Dδ2 or Dδ3 segments fused predominantly to Jα29. For IGH-JH, 329 clonal rearrangements were identified in 172 of 183 samples (94%) including novel types of V(D)J joining. Oligoclonality was found in ~1/3 (n = 57/183) of ALL samples. Genomic breakpoints were identified in 71 BCP-ALL. A distinct MRD high-risk subgroup of IGH-V(D)J-germline ALL revealed frequent deletions of IKZF1 (n = 7/11) and the presence of genomic fusions (n = 10/11). Quantitative measurement using genomic fusion breakpoints achieved equivalent results compared to conventional V(D)J-based MRD testing and could be advantageous upon persistence of a leukemic clone. Taken together, selective gc-HTS expands the spectrum of suitable MRD targets and allows for the identification of genomic fusions relevant to risk and treatment stratification in childhood ALL.
Databáze: MEDLINE