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Retinoblastoma genetics. The cancer can initiate with a germline RB1 mutation followed by a single somatic hit, or with two somatic mutations (M1 and M2). Loss of RB1 leads to the benign retinoma; further mutations (M3 to Mn) are required for malignancy. Retinoblastoma can also initiate by amplification of MYCN, with other genomic changes as yet unknown.
