RB1 and metastatic neoplasm: However, the majority of metastatic tumors demonstrated an increased somatic point mutation burden relative to their matched primary tumors (6/10) with 4/10 showing acquisition in the metastasis of candidate driver mutations not present in the matched primary (such as likely pathogenic TP53 or RB1 mutations), consistent with a model of branching clonal evolution and intra-patient heterogeneity.