Fig. 1

Genetic variants in RB1 and MYCN. a Mutations in RB1 have been found in the promoter region, affecting transcription, in coding regions, introducing premature stop-codons, and in introns, affecting splicing. Hot-spots do exist but only make up ~ 40% of all known mutations. Besides the introduction of premature stop-codons there are also three binding regions where amino acid substitutions can affect the binding ability. As these domains interact with different factors one may end up with a situation where proliferation is affected but not apoptosis, thereby affecting the penetrance and severity of retinoblastoma. b MYCN amplification is a common trait of retinoblastoma. Here, the difference in the size of the region duplicated, and the number of copies, affect tumor progression