Three of seven NF1-related tumors, including six plexiform neurofibromas and one peripheral nerve sheath tumor, showed secondary somatic genomic alterations in NF1. Pathogenic germline variants in RB1 (n = 1), SMARCB1 (n = 1), and TP53 (n = 2) were similarly associated with secondary somatic events in a pontine glioma, rhabdoid tumor, and glioblastoma multiforme and osteosarcoma, respectively. This evidence concerns the gene RB1 and plexiform neurofibroma.