Question

5a. Hereditary retinoblastoma generally affects children in both eyes, while spontaneous retinoblastoma usually occurs during adulthood and only in one eye. Explain the genetic basis for the epidemiologic distinction between these two forms of retinoblastoma.

b. Explain the apparent paradox: loss-of-function mutations in tumor-suppressor genes act recessively, yet hereditary retinoblastoma is inherited as an autosomal dominant.

Answer 1

A. In hereditary retinoblastoma, mutations in the RB1 gene appear to be inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to increase the risk of cancer.

A child who has sporadic (non-heritable) retinoblastoma develops only one tumour in one eye. This type of retinoblastoma is often found when the child is slightly older compared with those who have the heritable form.

B. the presence of a mutation at the susceptibility locus was argued to be insufficient for tumour formation, and a second somatic mutation was hypothesized to be necessary for promoting tumour formation. Loss of heterozygosity for chromosome 13, and specifically for the region of chromosome 13 containing the RB1 gene, occurred via a number of different mechanisms. In addition, through the study of inherited cases, it was shown that the copy of chromosome 13 retained in the tumor cells was derived from the affected parent and that the chromosome carrying the wild-type RB1 allele had been lost.