RB1 (retinoblastoma 1) is a key negative regulator of the G1 to S transition during cell division. Simple variants in RB1 are seen in about 3% of all tumors, including all retinoblastomas and ~10% of soft tissue and urinary tract tumors. Germline variants in RB1 may diagnose the retinoblastoma syndrome. Inactivation of RB1 and loss of RB1 tumor suppressor function has been identified in many early stage cancers.