2 who found no retinoblastomas with MYCN amplification among 93 tumors with two mutations in RB1 (RB1−/−). Further investigations into alternate mechanisms of inactivation of the RB1 gene product demonstrated phosphorylation of pRb at S608 in tumors without coding sequence mutations in one or both alleles of RB1 which is consistent with the observation that phosphorylation is the most common mechanism of pRb inactivation in most known cancers 22, 23. Here, RB1 is linked to retinoblastoma.