title: Suppression of RIZ in biologically unfavourable neuroblastomas.
abstract: Neuroblastoma is a paediatric solid tumor characterized by recurrent genomic abnormalities of prognostic importance. One of the most commonly observed abnormalities is deletion of the short arm of chromosome 1 and reduced expression of cancer related genes in this chromosomal arm. The long isoform of the retinoblastoma protein-interacting zink finger gene (RIZ1) is a known tumor suppressor and a candidate neuroblastoma gene located at 1p36.2. The present study was undertaken to further assess the possible involvement of RIZ in neuroblastoma development. Expression of RIZ transcripts were quantified in a panel of neuroblastoma cell lines and tumors (33 neuroblastomas and 3 ganglioneuromas). Methylation status of promoter P1 driving RIZ1 expression was quantified by bisulfite Pyrosequencing. Only low mean levels of promoter methylation (<10%) were observed in all samples. However, RIZ1 and RIZ1+2 mRNA were significantly under-expressed in biologically unfavourable tumors characterized by 1p loss (p<0.005) or MYCN amplification (p<0.005). Suppression of RIZ1 is likely to contribute to the pathogenesis of biologically unfavourable neuroblastomas. In contrast to multiple other neoplasias, RIZ1 promoter methylation is not a common event in neuroblastoma.
authors.affiliation: Department of Molecular Medicine and Surgery, KI, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. janos.geli@ki.se
authors.forename: Janos
authors.initials: J
authors.lastname: Geli
authors.forename: Nimrod
authors.initials: N
authors.lastname: Kiss
authors.forename: Per
authors.initials: P
authors.lastname: Kogner
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human