This pattern of mutational events points to a 4-hit/3-step model of tumorigenesis in patients with SMARCB1-positive schwannomatosis (Fig. 3a): The first hit (and step) represents the germline SMARCB1 mutation, whereas the second step involves LOH of 22q that removes the wild-type SMARCB1 allele and one of the two NF2 alleles. This evidence concerns the gene NF2 and schwannomatosis.