Mutations and allelic loss of the NF2 gene in neurofibromatosis 2-associated skin tumors

Schwannomas in the skin are frequently observed in neurofibromatosis 2 pati ents. In about one-quarter of the cases, skin tumors are the first clinical symptoms of this disease. Recognizing neurofibromatosis-2-related skin tum ors is therefore important for early diagnosis of neurofibromatosis 2, espe cially in pediatric patients. In this study, we examined 40 skin tumors (36 schwannomas and four neurofibromas) from 20 neurofibromatosis 2 patients f or NF2 mutations and allelic loss. NF2 mutations have been identified in bl ood from 15 (75%) of the 20 patients. We found NF2 mutations in five (13%) and NF2 allelic loss in 18 (45%) of the 40 analyzed tumors. Genetic alterat ions (allelic loss or mutation) were thus found in 50 (63%) out of the tota l of 80 examined alleles. In 17 (43%) tumors, alterations were found on bot h NF2 alleles. These results suggest that, as in the case of vestibular sch wannomas and meningiomas, loss of functional NF2 gene product is also the c ritical event in the development of skin schwannomas. Identification of gen etic alterations of the NF2 gene in skin tumors may help to identify neurof ibromatosis-2-associated skin tumors, thus assisting in the diagnosis of ne urofibromatosis 2 in ambiguous cases, and excluding neurofibromatosis 1 in unclear cases. We also report that the detection rate of constitutional mut ations was higher in patients with skin tumors (65%) than in patients witho ut skin tumors (40%).