Suppression of RIZ in biologically unfavourable neuroblastomas

Int J Oncol. 2010 Nov;37(5):1323-30. doi: 10.3892/ijo_00000784.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • DNA Methylation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Histone-Lysine N-Methyltransferase / genetics*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Molecular Sequence Data
  • Neoplasm Staging
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Histone-Lysine N-Methyltransferase
  • PRDM2 protein, human