Loss of heterozygosity on chromosome 22 in human gliomas does not inactivate the neurofibromatosis type 2 gene
The molecular genetic alterations that underlie development of gliomas, the most common neoplasm of the human central nervous system, include activation of cellular proto-oncogenes as well as inactivation of tumor suppressor genes. Although research has identified some affected loci, others clearly remain to be identified. We have investigated loss of heterozygosity on chromosome 22 in a panel of sporadic gliomas, and have assessed the possibility that inactivation of the neurofibromatosis type 2 (NF2) tumor suppressor gene on 22q plays a role in development of sporadic gliomas in humans. Loss of heterozygosity for loci on chromosome 22 loci was observed in 15 of 47 informative blood-tumor pairs, although no common area of loss of heterozygosity shared by all of these tumors could be identified. The most frequently affected segment, distal to the NF2 locus and bounded proximally by D22S15 and distally by a gene for myoglobin, was shared by as many as 11 tumors. Loss of heterozygosity at the NF2 locus was observed in 10 tumors. No rearrangements of the NF2 gene could be detected by Southern analysis of restriction endonuclease-digested genomic DNA, and no abnormally migrating bands were detected on single strand conformation analysis of individual exons of the NF2 gene. Thus, although frequent loss of heterozygosity on chromosome 22 suggests that inactivation of a tumor suppressor gene on this chromosome plays a role in development of gliomas, there is no evidence that inactivation of the NF2 gene is implicated in this process, confirming the results of other studies of the NF2 gene in human gliomas. The identity of the putative tumor suppressor gene on 22q involved in development of gliomas remains unknown.