A group of schwannomas with interstitial deletions on 22q located outside the NF2 locus shows no detectable mutations in the NF2 gene

Schwannomas are tumors arising mainly at cranial and spinal nerves. Bilater al vestibular schwannoma is the hallmark of neurofibromatosis type2 (NF2). The NF2 gene has been cloned and comprehensive analysis of its mutations in schwannomas shows chat up to 60% of tumors carry inactivating mutations. T hus, the genetic mechanism behind the development of more than 40% of schwa nnomas without NF2 mutations is unknown. We have therefore studied tumor ti ssue from 50 human schwannomas by allelotyping and have found chromosome 22 deletions in over 80% of the cases. We detected 14 cases (27%) that reveal ed partial deletions of one copy of chromosome 22, i.e., terminal and/or in terstitial deletions. We sequenced the NF2 gene in seven of these tumors an d detected only one case with mutations. The deletion mapping of chromosome 22 in tumors with partial deletions indicates that several regions, in add ition to the NF2 locus, harbor genes involved in schwannoma tumorigenesis. Our findings suggest that heterogeneity in the mechanisms leading to the de velopment of schwannomas probably exists. These findings are in agreement w ith the recent analysis of schwannomas from familial and sporadic cases of schwannomatosis and point to a possible role of an additional gene, which, in cooperation with the NF2 tumor suppressor, causes schwannomas.