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

ABSTRACT: 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 TR?, a total of 300 clonal rearrangements were detected in 158 of 183 samples (86%). Beside clonal V?2-D?3, D?2-D?3, and V?2-J? we identified a novel group of recurrent D?-J? rearrangements, comprising D?2 or D?3 segments fused predominantly to J?29. 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.

SUBMITTER: Zur Stadt U 

PROVIDER: S-EPMC6884523 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature