title: Tumour induction by the retinoblastoma mutation is independent of N-myc expression.
abstract: Retinoblastoma (RB) tumours form in the eyes of young children when homozygosity for a mutation at the Rb-1 locus develops in a somatic retinal cell. A similar shift to homozygosity for the RB mutation has been observed in osteogenic sarcoma (OS) tumours that commonly arise as second tumours in children who survive RB. This observation suggests that the Rb-1 locus controls the expression of genes with oncogenic potential; a possible target is the oncogene N-myc, which is sometimes amplified and over-expressed in the neuroectodermal tumours neuroblastoma and RB. However, N-myc is developmentally regulated in normal murine embryogenesis, and an alternative possibility is that the expression of the gene in tumour cells reflects their embryonic origin and is unrelated to the RB mutation. We have therefore examined N-myc expression in various fetal, adult and tumour tissues, and report here that the gene is expressed in fetal but not in adult brain and retina and in near-diploid RB tumour samples at levels similar to those observed in normal fetal retina. Only RB tumours with genomic amplification of the N-myc gene exhibited increased levels of expression; and no N-myc transcripts were detected in osteogenic sarcomas initiated by mutations at the Rb-1 locus. We therefore conclude that the expression of N-myc in RB tumours probably reflects the origin of the tumour from an embryonic tissue normally expressing the gene and is not directly associated with the mutation at the RB locus.
mesh_terms: D000818:Animals; D001921:Brain; D002460:Cell Line; D002478:Cells, Cultured; D005333:Fetus; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D012516:Osteosarcoma / Q000235:genetics; D012313:RNA / Q000032:analysis; D012160:Retina; D012175:Retinoblastoma / Q000235:genetics*
chemical_list: D012313:RNA