title: NB4S, a member of the TBC1 domain family of genes, is truncated as a result of a constitutional t(1;10)(p22;q21) chromosome translocation in a patient with stage 4S neuroblastoma.
abstract: Molecular cloning of the breakpoints of a t(1;10)(p22q21) constitutional translocation breakpoint in a patient with stage 4S neuroblastoma has identified two genes which are fused in-frame to generate a novel gene. The 1p22 gene, which we have called NB4S , encodes a 7.5 kb transcript with an 810 amino acid open reading frame and is expressed in a wide variety of tissues. NB4S has >88% homology with the mouse EVI -5 gene within the coding region and shows strong homology over a 200 amino acid region with TBC1 box motif genes involved in cell growth and differentiation. The C-teminal end of the protein contains a number of coiled coil domains, indicating a possible protein-protein binding function. The chromosome 10 breakpoint interrupts a novel transcript (TRNG10) which could only be detected in tumor cells. This transcript has no exon/intron structure or significant open reading frame, suggesting that it is a structural RNA which is transcribed but not translated. The chromosome rearrangement creates a fusion gene product which combines the TBC1 motif of NB4S with a polyadenylation signal from TRNG10 , potentially generating a truncated protein with oncogenic properties.
authors.affiliation: Department of Neurosciences-NC30, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: T
authors.initials: T
authors.lastname: Roberts
authors.forename: O
authors.initials: O
authors.lastname: Chernova
authors.forename: J K
authors.initials: JK
authors.lastname: Cowell
mesh_terms: D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003001:Cloning, Molecular; D020690:GTPase-Activating Proteins; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C105043:Evi5 protein, mouse; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C095906:Tbc1d1 protein, mouse; D014157:Transcription Factors