RB1 and cancer: In 1971, Knudson elegantly described the genetic mechanism of RB with his “two-hit hypothesis”.5 This ultimately led to the description, localization, and cloning of the first tumor suppressor gene, which we today recognize as RB1. Ironically, despite the pioneering role RB has played in cancer genomics, the children who are affected by RB have not received many of the benefits that precision oncology has to offer.