title: Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene.
abstract: We have characterised the DFFB gene, encoding the active subunit of the apoptotic nuclease DNA fragmentation factor (DFF40). DFFB maps to 1p36, near the imprinted putative tumour suppressor gene TP73. The DFFA gene (encoding the inhibitory DFF45 subunit) also maps to 1p36.2-36.3, and we show by FISH that DFFB lies distal to DFFA. We have also mapped a processed DFFB pseudogene to chromosome 9. DFFB itself has seven coding exons spanning 10 kb. Exhaustive mutation screening of 41 neuroblastomas and other tumours in which a 1p36 tumour suppressor gene is implicated showed no tumour-specific mutations. A coding region polymorphism was used to demonstrate uniformly biallelic expression in human fetal DFFB transcripts. Since the putative neuroblastoma tumour suppressor gene in distal 1p36 is predicted to be maternally expressed, the lack of imprinting and absence of somatic mutations in DFFB indicate that it is probably not the neuroblastoma tumour suppressor gene.
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital, UK.
authors.forename: H
authors.initials: H
authors.lastname: Judson
authors.forename: N
authors.initials: N
authors.lastname: van Roy
authors.forename: L
authors.initials: L
authors.lastname: Strain
authors.forename: J
authors.initials: J
authors.lastname: Vandesompele
authors.forename: M
authors.initials: M
authors.lastname: Van Gele
authors.forename: F
authors.initials: F
authors.lastname: Speleman
authors.forename: D T
authors.initials: DT
authors.lastname: Bonthron
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D015266:Carcinoma, Merkel Cell / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D020451:Contig Mapping; D053938:DNA Fragmentation / Q000235:genetics*; D003851:Deoxyribonucleases / Q000235:genetics*; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor; D005820:Genetic Testing; D018392:Genomic Imprinting; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D019656:Loss of Heterozygosity; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D012326:RNA Splicing; D017384:Sequence Deletion
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; C109664:caspase-activated DNase inhibitor; C113696:DFFB protein, human; D003851:Deoxyribonucleases; D020169:Caspases