title: Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16).
abstract: 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.
authors.affiliation: Department of Human Genetics, Leiden University, The Netherlands.
authors.forename: R H
authors.initials: RH
authors.lastname: Giles
authors.forename: J G
authors.initials: JG
authors.lastname: Dauwerse
authors.forename: C
authors.initials: C
authors.lastname: Higgins
authors.forename: F
authors.initials: F
authors.lastname: Petrij
authors.forename: J W
authors.initials: JW
authors.lastname: Wessels
authors.forename: G C
authors.initials: GC
authors.lastname: Beverstock
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.forename: M
authors.initials: M
authors.lastname: Jotterand-Bellomo
authors.forename: J H
authors.initials: JH
authors.lastname: Falkenburg
authors.forename: R M
authors.initials: RM
authors.lastname: Slater
authors.forename: G J
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: B A
authors.initials: BA
authors.lastname: van der Reijden
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D015139:Blotting, Southern; D050882:CREB-Binding Protein; D002885:Chromosomes, Human, Pair 16; D002898:Chromosomes, Human, Pair 8; D015321:Gene Rearrangement; D051548:Histone Acetyltransferases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human