A new tumor suppressor gene responsible for type 2 neurofibromatosis is inactivated in neurinoma and meningioma

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes to multiple schwannomas, meningiomas and to a lesser extent, to ependymomas. These tumours have been shown to display frequent loss of chromosome 22. Gene defect causing NF2 has been mapped on chromosome 22. Using positional cloning, we and others recently isolated the gene responsible for NF2. Its product displays strong homology with membrane organizing protein suggesting that this protein, called either Schwannomin or Merlin, could act as a bridge between membrane and cytoskeleton. Alterations of the NF2 gene have been identified in NF2 patients and result usually in a truncated, presumably inactive protein. Analysis of tumoral DNA from sporadic schwannomas and meningiomas demonstrates complete loss of function in many cases, providing evidence that the NF2 gene acts as tumor suppressor gene. As a consequence, genetic presymptomatic diagnosis of at risk individuals for NF2 is now possible.