Somatic oncogenic activating mutations in FGFR3 and/or PIK3CA have recently been described in benign epithelial cutaneous lesions that never progress to malignancy (seborrheic keratoses and epidermal nevi).
Therefore, we examined exons 9 and 20 of PIK3CA and FGFR3 hotspot mutations in EN (n = 33) and SK (n = 62), two proliferative skin lesions lacking malignant potential.
Molecular analysis of a biopsy specimen obtained from the epidermal nevus revealed a heterozygous R248C hotspot mutation in FGFR3, whereas in normal skin the FGFR3 wild-type allele was exclusively found.
Recently, the same FGFR3 mutations known from skeletal dysplasia syndromes and urothelial carcinoma have been shown to cause benign human skin tumors such as seborrheic keratoses and epidermal nevi.
The association of epidermal nevi and transitional cell bladder carcinoma may be linked to a mutation in the fibroblast growth factor receptor 3 gene, FGFR<sub>3</sub>, but a clear link has yet to be substantiated and additional molecular studies are needed.
Somatic oncogenic activating mutations in FGFR3 and/or PIK3CA have recently been described in benign epithelial cutaneous lesions that never progress to malignancy (seborrheic keratoses and epidermal nevi).
Genetic evaluation revealed a heterozygote mutation in the HRAS gene in both the keratinocytic epidermal nevus and thymoma but not in DNA extracted from blood lymphocytes, thus establishing the mutation as postzygotic.
We studied the K1 and K10 genes in blood and in the keratinocytes and fibroblasts of lesional and nonlesional skin from three patients with epidermal nevi and four of their offspring with epidermolytic hyperkeratosis.
Since 1994, four cases of epidermal nevus with epidermolytic hyperkeratosis (EH) caused by keratin 10 gene mutations have been reported, although no keratin 1 (K1) gene mutation has yet been reported.
An identical postzygotic HRAS mutation was shown to be present in both keratinocytic epidermal nevus and thymoma and to be associated with bone lesions and hypophosphatemia due to elevated FGF23 levels.
These include disorders of DNA replication/repair functions (Bloom, Werner, Rothmund-Thomson and Muir-Torre syndromes), genodermatoses affecting the folliculo-sebaceus unit (Brooke-Spiegler, Schöpf-Schulz-Passarge and Cowden syndromes), immune response (cartilage-hair hypoplasia and epidermodysplasia verruciformis) and melanin biosynthesis (oculocutaneous albinism and Hermansky-Pudlak syndrome), and some epidermal nevus syndromes.