OS incidence is increased several hundred-fold in patients with RB1 germline mutations and patients with hereditary retinoblastoma through loss of the Rb tumor suppressor protein, a key regulator of E2F transcription factors and cell cycle progression, and thus its deletion is often accompanied by defects in cell cycle exit and can result in an undifferentiated cellular phenotype [9–11]. This evidence concerns the gene RB1 and retinoblastoma.