Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma.

Through family studies and analysis of patients with congenital chromosome abnormalities, the germ-line mutation responsible for the hereditary form of the eye tumour, retinoblastoma, has been assigned to the q14 region on chromosome 13 and closely linked to an enzyme called esterase D (ESD). Knudson has proposed that as few as one somatic event in addition to the germ-line mutation is required to induce tumours in patients with the hereditary form of retinoblastoma; the non-hereditary form requires two somatic events to occur in the same cell. The somatic event(s) may involve either mutation of the remaining normal gene at 13q14 or mutation of a gene at another site in the genome. Here we have examined six retinoblastoma patients who are heterozygous for electrophoretic variants of ESD. Although the normal cells of all six patients expressed both variants, the tumour cells of four patients expressed enzyme from only one of the two ESD alleles. We tentatively conclude that induction of a retinoblastoma tumour requires the somatic inactivation of genes near the ESD locus including the remaining normal gene at the retinoblastoma (RB) locus.