Bruno Almeida Lopes, Claus Meyer, Thayana Conceição Barbosa, Udo Zur Stadt, Martin Horstmann, Nicola C. Venn, Susan Heatley, Deborah L. White, Rosemary Sutton, Maria S. Pombo-de-Oliveira, Rolf Marschalek, Mariana Emerenciano
- IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in childhood B-cell precursor acute lymphoblastic leukemia. Because of its clinical importance, we previously mapped breakpoints of intragenic deletions and developed a multiplex PCR assay to detect recurrent intragenic ΔIKZF1. Since the multiplex PCR was not able to detect complete deletions (IKZF1 Δ1-8), which account for ~30% of all ΔIKZF1, we aimed at investigating the genomic scenery of IKZF1 Δ1-8. Six samples of cases with IKZF1 Δ1-8 were analyzed by microarray assay, which identified monosomy 7, isochromosome 7q, and large interstitial deletions presenting breakpoints within COBL gene. Then, we established a multiplex ligation-probe amplification (MLPA) assay and screened copy number alterations within chromosome 7 in 43 diagnostic samples with IKZF1 Δ1-8. Our results revealed that monosomy and large interstitial deletions within chromosome 7 are the main causes of IKZF1 Δ1-8. Detailed analysis using long distance inverse PCR showed that six patients (16%) had large interstitial deletions starting within intronic regions of COBL at diagnosis, which is ~611 Kb downstream of IKZF1, suggesting that COBL is a hotspot for ΔIKZF1. We also investigated a series of 25 intragenic deletions (Δ2–8, Δ3–8 or Δ4–8) and 24 relapsed samples, and found one IKZF1-COBL tail-to-tail fusion, thus supporting that COBL is a novel hotspot for ΔIKZF1. Finally, using RIC score methodology, we show that breakpoint sequences of IKZF1 Δ1-8 are not analog to RAG-recognition sites, suggesting a different mechanism of error promotion than that suggested for intragenic ΔIKZF1.
MetadatenAuthor: | Bruno Almeida Lopes, Claus MeyerORCiDGND, Thayana Conceição Barbosa, Udo Zur Stadt, Martin Horstmann, Nicola C. Venn, Susan Heatley, Deborah L. White, Rosemary Sutton, Maria S. Pombo-de-OliveiraORCiD, Rolf MarschalekORCiDGND, Mariana Emerenciano |
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URN: | urn:nbn:de:hebis:30:3-455538 |
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DOI: | https://doi.org/10.18632/oncotarget.10590 |
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ISSN: | 1949-2553 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/27419633 |
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Parent Title (English): | OncoTarget |
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Publisher: | Impact Journals LLC |
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Place of publication: | [s. l.] |
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Document Type: | Article |
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Language: | English |
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Year of Completion: | 2016 |
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Date of first Publication: | 2016/07/13 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2018/01/25 |
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Tag: | COBL; IKZF1; RAG; acute lymphoblastic leukemia; relapse |
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Volume: | 7 |
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Issue: | 33 |
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Page Number: | 10 |
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First Page: | 53064 |
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Last Page: | 53073 |
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Note: | All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. |
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HeBIS-PPN: | 426121430 |
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Institutes: | Biochemie, Chemie und Pharmazie / Pharmazie |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 3.0 |
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