Expression and amplification of the N-myc gene in primary retinoblastoma.

Retinoblastoma, the most common intraocular tumour of childhood, probably arises from embryonal cells and occurs in hereditary and non-hereditary forms. Recent evidence suggests that this retinoblastoma (Rb) susceptibility gene located at chromosome 13q14 is actually recessive. Knudson has proposed that the tumour is caused by two mutational events. This idea was extended by Comings, who suggested that dominantly inherited tumours may result from loss or inactivation of both alleles of regulatory or suppressor genes that, when active, prevent the expression of a structural transforming gene(s) (possibly an oncogene) normally active only during embryogenesis. Despite circumstantial evidence for this hypothesis, no activated oncogene has been identified. We now report that (1) the N-myc gene is amplified 10-200-fold in two primary retinoblastomas and a retinoblastoma cell line Y79 and (2) expression of N-myc gene is highly elevated in most of the retinoblastomas examined. This finding suggests that N-myc gene may have a primary role in the tumorigenesis of retinoblastoma.