RB1 and cancer: This event is followed, as in other cancers, by the sequential acquisition of additional genetic abnormalities that define the course leading to tumor formation and metastasis.19–24 Genomic instability contributes to the progression of retinoma to malignant RB.25–27 In humans, this progression is characterized by loss of both copies of the RB1 gene in retinoma followed by changes in the copy number of oncogenes such as MYCN (2p24.3), E2F3 and DEK (6p22), KLF14 (7q32), and MDM4 (1q32) as well as tumor suppressor genes CDH11 (16q21) and p75NTR (17q21).