Mutations were commonly found in genes known to directly control RBL2/pRb activity during G1/S phase transition, such as Cyclin D1, E2Fs, and CDK4 (average CNA frequency for G1/S regulators in Cluster 2 = 0.601; Supplementary Fig. 9j), all of which are known to be associated with aggressive breast tumours and among the most frequent driver genes18,81. The gene discussed is CDK4; the disease is breast neoplasm.