title: Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma consensus deletion region 1p36.3-->p36.2, but absence of mutations in primary tumors.
abstract: The processed product of the human gene preprocortistatin, the peptide cortistatin-17 (hCST-17), bears a strong structural resemblance to the peptide somatostatin (SST), which has an identical receptor binding domain. CST has affinity to all known SST receptor (SSTR) subtypes. Expression of both SST and its receptors has been shown in previous studies to have biological and clinical significance in neuroblastomas, with a putative role in tumor differentiation and apoptosis in vivo. In this work we have employed radiation hybrid mapping and BAC physical mapping to map the human preprocortistatin gene (CORT) to chromosome region 1p36.3-->p36.2, close to the genetic marker D1S244. D1S244 defines the centromeric border of the smallest region of overlap of deletion in our primary neuroblastoma material. We have also defined the genomic sequence of the gene by BAC sequencing and found that preprocortistatin consists of two exons divided by a 1-kb intron. Two polymorphic sites, neither of which causes amino acid exchange, have been detected in the coding region of the gene. Expression studies showed that preprocortistatin is expressed in neuroblastomas of all different stages, as well as in ganglioneuromas. Through genomic sequencing we made mutation analyses of exonic sequences in 49 primary neuroblastomas of all different stages, but no mutations could be detected.
authors.affiliation: Department of Clinical Genetics, Gothenburg University, Sahlgrenska University Hospital/East, Gothenburg, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Ejeskär
authors.forename: F
authors.initials: F
authors.lastname: Abel
authors.forename: R
authors.initials: R
authors.lastname: Sjöberg
authors.forename: J
authors.initials: J
authors.lastname: Bäckström
authors.forename: P
authors.initials: P
authors.lastname: Kogner
authors.forename: T
authors.initials: T
authors.lastname: Martinsson
mesh_terms: D001483:Base Sequence; D002648:Child; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D016384:Consensus Sequence / Q000235:genetics*; D020451:Contig Mapping; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D008126:Lod Score; D019656:Loss of Heterozygosity / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger; C099323:cortistatin; C107518:preprocortistatin