Furthermore, they are commonly associated with family cancer syndromes such as retinoblastoma, where a first mutation (first hit) occurs in the first allele of the retinoblastoma (Rb) gene in germinal cells, and a second mutation (second hit) is acquired in the second allele of the Rb gene in somatic cells and is responsible for the loss of function of the Rb protein. Here, RB1 is linked to retinoblastoma.