IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia
| Autor: | Nicola C. Venn, Christine J. Harrison, Sanjeev Gupta, Claus Meyer, Gianni Cazzaniga, Rolf Marschalek, Caroline Pires Poubel, Chiara Palmi, Sameer Bakhshi, Nicolas Duployez, Grigory Tsaur, Rosemary Sutton, Marcela B. Mansur, Thayana Conceição Barbosa, Matthew Bashton, Udo zur Stadt, Mariana Emerenciano, Maria S. Pombo-de-Oliveira, Bruno Almeida Lopes, Cristina N. Alonso, Martin A. Horstmann |
|---|---|
| Přispěvatelé: | Lopes, B, Meyer, C, Barbosa, T, Poubel, C, Mansur, M, Duployez, N, Bashton, M, Harrison, C, zur Stadt, U, Horstmann, M, Pombo-de-Oliveira, M, Palmi, C, Cazzaniga, G, Venn, N, Sutton, R, Alonso, C, Tsaur, G, Gupta, S, Bakhshi, S, Marschalek, R, Emerenciano, M |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Translational Oncology Translational Oncology, Vol 12, Iss 5, Pp 726-732 (2019) |
| ISSN: | 1936-5233 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|