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IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia
- Source :
- Translational Oncology, Translational Oncology, Vol 12, Iss 5, Pp 726-732 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Chromosome 7 (human)
Genetics
Cancer Research
Original article
Breakpoint
breakpoint cluster region
Intron
Biology
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
A400
lcsh:RC254-282
B900
03 medical and health sciences
ETV6
Leukemia
030104 developmental biology
0302 clinical medicine
Oncology
CDKN2A
030220 oncology & carcinogenesis
medicine
Recombination signal sequences
ddc:610
Subjects
Details
- Language :
- English
- ISSN :
- 19365233
- Database :
- OpenAIRE
- Journal :
- Translational Oncology, Translational Oncology, Vol 12, Iss 5, Pp 726-732 (2019)
- Accession number :
- edsair.doi.dedup.....6938c483712f36605107da6250ef4268