title: A constitutional translocation t(1;17)(p36.2;q11.2) in a neuroblastoma patient disrupts the human NBPF1 and ACCN1 genes.
abstract: The human 1p36 region is deleted in many different types of tumors, and so it probably harbors one or more tumor suppressor genes. In a Belgian neuroblastoma patient, a constitutional balanced translocation t(1;17)(p36.2;q11.2) may have led to the development of the tumor by disrupting or activating a gene. Here, we report the cloning of both translocation breakpoints and the identification of a novel gene that is disrupted by this translocation. This gene, named NBPF1 for Neuroblastoma BreakPoint Family member 1, belongs to a recently described gene family encoding highly similar proteins, the functions of which are unknown. The translocation truncates NBPF1 and gives rise to two chimeric transcripts of NBPF1 sequences fused to sequences derived from chromosome 17. On chromosome 17, the translocation disrupts one of the isoforms of ACCN1, a potential glioma tumor suppressor gene. Expression of the NBPF family in neuroblastoma cell lines is highly variable, but it is decreased in cell lines that have a deletion of chromosome 1p. More importantly, expression profiling of the NBPF1 gene showed that its expression is significantly lower in cell lines with heterozygous NBPF1 loss than in cell lines with a normal 1p chromosome. Meta-analysis of the expression of NBPF and ACCN1 in neuroblastoma tumors indicates a role for the NBPF genes and for ACCN1 in tumor aggressiveness. Additionally, DLD1 cells with inducible NBPF1 expression showed a marked decrease of clonal growth in a soft agar assay. The disruption of both NBPF1 and ACCN1 genes in this neuroblastoma patient indicates that these genes might suppress development of neuroblastoma and possibly other tumor types.
authors.affiliation: Department for Molecular Biomedical Research, VIB, Ghent, Belgium.
authors.forename: Karl
authors.initials: K
authors.lastname: Vandepoele
authors.forename: Vanessa
authors.initials: V
authors.lastname: Andries
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.forename: Katrien
authors.initials: K
authors.lastname: Staes
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laureys
authors.forename: Els
authors.initials: E
authors.lastname: De Smet
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.forename: Frans
authors.initials: F
authors.lastname: van Roy
mesh_terms: D062565:Acid Sensing Ion Channels; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D017931:DNA Primers; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: C568424:ASIC2 protein, human; D062565:Acid Sensing Ion Channels; D017931:DNA Primers; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; C521186:NBPF3 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins