RB1 and neoplasm: Recurrent inactivation of retinoblastoma protein 1 (RB1), another major tumor suppressor and cell-cycle regulator downstream EGFR, has also been detected in LAC, either due to mutation of the RB1 gene itself, or deletion/mutation/methylation of other cell cycle-related tumor suppressor genes, such as CDKN2A, or mutation/amplification of cell cycle-inducing proto-oncogenes, such CCND1/2, CCNE1, CDK4/6 [3,10,12,40].