Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16)
| Autor: | B. A. Van Der Reijden, Hartmut Döhner, J. H. F. Falkenburg, G.J.B. van Ommen, Fred Petrij, M Jotterand-Bellomo, J. G. Dauwerse, C. Higgins, Geoffrey C. Beverstock, Martijn H. Breuning, Rachel H. Giles, J. W. Wessels, Rosalyn Slater, A. Hagemeijer |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Biology Translocation Genetic Acetyltransferases Complementary DNA medicine Humans In Situ Hybridization Fluorescence Histone Acetyltransferases Southern blot Gene Rearrangement Genetics Contig medicine.diagnostic_test breakpoint cluster region Nuclear Proteins Hematology Gene rearrangement CREB-Binding Protein Molecular biology Blotting Southern Leukemia Myeloid Acute Oncology Fusion transcript Trans-Activators Cosmid Chromosomes Human Pair 16 Chromosomes Human Pair 8 Transcription Factors Fluorescence in situ hybridization |
| Zdroj: | Leukemia. 11:2087-2096 |
| ISSN: | 1476-5551 0887-6924 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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