Gene for retinoblastoma is located on
harshmohan textbook of pathology 7th edition. *autosomal dominant trait by retinoblastoma susceptibility gene located on chromosome 13. RB Gene: Governor of the Cell Cycle It is useful to begin with the retinoblastoma gene (RB), the first tumor suppressor gene to be discovered and, as it happens, a prototypical representative. As with many advances in medicine, the discovery of tumor suppressor genes was accomplished by the study of a rare disease--in this case, retinoblastoma, an uncommon childhood tumor. Approximately 60% of retinoblastomas are sporadic, and the remaining ones are familial, the predisposition to develop the tumor being transmitted as an autosomal dom- inant trait. To account for the sporadic and familial occur- rence of an identical tumor, Knudson, in 1974, proposed his now famous two-hit hypothesis, which in molecular terms can be stated as follows: * Two mutations (hits) are required to produce retinoblas- toma. These involve the RB gene, which has been mapped to chromosomal locus 13q14. Both of the normal alleles of the RB locus must be inactivated (hence the two hits) for the development of retinoblastoma (Fig. 5-21). * In familial cases, children inherit one defective copy of the RB gene in the germ line; the other copy is normal. Retinoblastoma develops when the normal RB gene is lost in retinoblasts as a result of somatic mutation. Because in retinoblastoma families only a single somatic mutation is required for expression of the disease, the familial transmission follows an autosomal dominant inheritance pattern. * In sporadic cases, both normal RB alleles are lost by somatic mutation in one of the retinoblasts. The end result is the same: a retinal cell that has lost both of the normal copies of the RB gene becomes cancerous. Ref Robbins 9/e pg 183
Chromosome 13
Chromosome 1
Chromosome 10
Chromosome 5
General pathology