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Lookup NU author(s): Dr Matthew BashtonORCiD, Professor Christine Harrison FRCPath FMedSci
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2019 The Authors IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial deletions (53%). The latter included COBL-r, which were found in 12% of the IKZF1 ∆1-8 cohort. Patients with COBL-r are mostly classified as intermediate cytogenetic risk and frequently harbor ETV6, PAX5, CDKN2A/B deletions. Overall, 56% of breakpoints were located within COBL intron 5. Cryptic recombination signal sequence motifs were broadly distributed within the sequence of COBL, and no enrichment for the breakpoint cluster region was found. In summary, a diverse spectrum of alterations characterizes ΔIKZF1 and they also include deletion breakpoints within COBL. We confirmed that COBL is a hotspot associated with ΔIKZF1, but these rearrangements are not driven by RAG-mediated recombination.
Author(s): Lopes BA, Meyer C, Barbosa TC, Poubel CP, Mansur MB, Duployez N, Bashton M, Harrison CJ, zur Stadt U, Horstmann M, Pombo-de-Oliveira MS, Palmi C, Cazzaniga G, Venn NC, Sutton R, Alonso CN, Tsaur G, Gupta SK, Bakhshi S, Marschalek R, Emerenciano M
Publication type: Article
Publication status: Published
Journal: Translational Oncology
Year: 2019
Volume: 12
Issue: 5
Pages: 726-732
Online publication date: 13/03/2019
Acceptance date: 11/02/2019
Date deposited: 27/03/2019
ISSN (print): 1936-5233
Publisher: Elsevier
URL: https://doi.org/10.1016/j.tranon.2019.02.002
DOI: 10.1016/j.tranon.2019.02.002
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