Isochromosome 6p, a unique chromosomal abnormality in retinoblastoma: verification by standard staining techniques, new densitometric methods, and somatic cell hybridization.

Study of chromosome rearrangements in retinoblastoma tumors revealed that all tumors contained either an unusual isochromosome and/or extra copies of chromosome 1q. Extra copies of chromosome 1q occur in many malignancies. The pattern of G-bands suggested that the isochromosome was derived from either the short arm of chromosome 6, i(6p), or the long arm of chromosome 17, i(17q). Standard staining techniques using G-, C-, Q-, and R-banding; high resolution G-banding; and density profile analysis were consistent with the characteristic isochromosome of retinoblastoma being i(6p), rather than i(17q). This conclusion was substantiated by the analysis of segregants derived from retinoblastoma X mouse hybrid cells which had been grown in bromodeoxyuridine to select for loss of chromosome 17. The unique isochromosome was not lost under these conditions confirming that it is an i(6p) rather than an i(17q). The i(6p) abnormality has not been observed frequently in other tumors, but occurs in 60% of retinoblastoma tumors. Thus, although the mutation predisposing to retinoblastoma is known to map at 13q14, somatic amplification of genes on 1q and 6p may play a role in the pathogenesis of this tumor.