MDM4 and retinoblastoma: MYC was also expressed, but at the lower level than MYCN, whereas MDM4 was expressed in all the cone clusters at higher levels compared to MDM2. Although mutations in RB1 are often considered as the key prerequisite for retinoblastoma initiation, further genetic changes that may activate oncogenes or inactivate tumor suppressor genes may drive the acquisition of the malignant phenotype.24