Genesis and genetics of retinoblastoma.

1. The increase in frequency of retinoblastoma reported during the last decades [FRANCOIS, 1968] is probably not due to an increase of the mutation rate but to a lowered mortality rate and also to improvement in methods of investigation and diagnosis. (2) In 95% of all affected families retinoblastoma occurs just once, the familial occurrence being +/- 5%. (3) The hereditary retinoblastomas (whether sporadic or familial) represent about 40% of all cases. (4) A new dominant mutation is judged to be responsible for 100% of the bilateral sporadic cases and for 10-20% of the unilateral sporadic cases. (5) Genetic susceptibility to cancer can be chromosomal, mendelian dominant, mendelian recessive, or polygenic. Retinoblastoma belongs to the first as well as to the second category. The fact that the chromosomal aberration of the D deletion syndrome antedates the appearance of the tumour suggests that chromosomal change may be the primary cause of the tumour formation. (6) Although several problems remain an unsolved question, attention must be given to KNUDSON'S working hypothesis [KNUDSON et al., 1973], according to which all childhood tumours fit at least a two-mutational aetiology, involving a two-step process. It remains an open question whether both events occur at different genetic loci or at alleles of the same locus. (7) The main difficulty in genetic counseling is the lack of means for identifying which sporadic retinoblastoma cases are due to new germinal mutations.