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Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)

The CREB-binding protein (CBP) is a large nuclear protein that regulates many signal transduction pathways and is involved in chromatin-mediated transcription. The translocation t(8;16)(p11;p13.3) consistently disrupts two genes: the CBP gene on chromosome band 16p13.3 and the MOZ gene on chromosome...

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Main Authors: Giles, Rachel Helen (Author) , Dauwerse, J. G. (Author) , Higgins, C. (Author) , Petrij, F. (Author) , Wessels, J. W. (Author) , Beverstock, G. C. (Author) , Döhner, Hartmut (Author) , Jotterand-Bellomo, M. (Author) , Falkenburg, J. H. F. (Author) , Slater, R. M. (Author) , van Ommen, G.-J. B. (Author) , Hagemeijer, A. (Author) , van der Reijden, B. A. (Author) , Breuning, M. H. (Author)
Format: Article (Journal)
Language:English
Published: 01 December 1997
In: Leukemia
Year: 1997, Volume: 11, Issue: 12, Pages: 2087-2096
ISSN:1476-5551
DOI:10.1038/sj.leu.2400882
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/sj.leu.2400882
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/2400882
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Author Notes:R.H. Giles, J. G. Dauwerse, C. Higgins, F. Petrij, J.W. Wessels, G.C. Beverstock, H. Döhner, M. Jotterand-Bellomo, J.H.F. Falkenburg, R.M. Slater, G.-J. B. van Ommen, A. Hagemeijer, B.A. van der Reijden, M.H. Breuning
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Summary:The CREB-binding protein (CBP) is a large nuclear protein that regulates many signal transduction pathways and is involved in chromatin-mediated transcription. The translocation t(8;16)(p11;p13.3) consistently disrupts two genes: the CBP gene on chromosome band 16p13.3 and the MOZ gene on chromosome band 8p11. Although a fusion of these two genes as a result of the translocation is expected, attempts at detecting the fusion transcript by reverse transcriptase polymerase chain reaction (RT-PCR) have proven difficult; to date, only one in-frame CBP/MOZ fusion transcript has been reported. We therefore sought other reliable means of detecting CBP rearrangements. We applied fluorescence in situ hybridization (FISH) and Southern blot analyses to a series of AML patients with a t(8;16) and detected DNA rearrangements of both the CBP and the MOZ loci in all cases tested. All six cases examined for CBP rearrangements have breakpoints within a 13 kb breakpoint cluster region at the 5′ end of the CBP gene. Additionally, we used a MOZ cDNA probe to construct a surrounding cosmid contig and detect DNA rearrangements in three t(8;16) cases, all of which display rearrangements within a 6 kb genomic fragment of the MOZ gene. We have thus developed a series of cosmid probes that consistently detect the disruption of the CBP gene in t(8;16) patients. These clones could potentially be used to screen other cancer-associated or congenital translocations involving chromosome band 16p13.3 as well.
Item Description:Gesehen am 30.10.2024
Physical Description:Online Resource
ISSN:1476-5551
DOI:10.1038/sj.leu.2400882

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