Secondary mutations were observed in all three of the skin tumors in which full NGS was performed, consistent with point mutation as a second hit event to eliminate normal function of TSC2. In one subject (P17), there was no enrichment for the mutation in the skin tumor biopsy, possibly due to the biopsy not penetrating the dermis (the site of the mutant fibroblasts), or the lesion not being a true TSC-related tumor. This evidence concerns the gene TSC2 and neoplasm.