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, includ e activation of cellular proto-oncogenes as well as inactivation of tu mor suppressor genes. Although research has identified some affected l oci, others clearly remain to be identified. We have investigated loss of heterozygosity on chromosome 22 in a panel of sporadic gliomas, an d have assessed the possibility that inactivation of the neurofibromat osis type 2 (NF2) tumor suppressor gene on 22q plays a role in develop ment of sporadic gliomas in humans. Loss of heterozygosity for loci on chromosome 22 loci was observed in 15 of 47 informative blood-tumor p airs, although no common area of loss of heterozygosity shared by all of these tumors could be identified. The most frequently affected segm ent, distal to the NF2 locus and bounded proximally by D22S15 and dist ally by a gene for myoglobin, was shared by as many as 22 tumors. Loss of heterozygosity at the NF2 locus was observed in 10 tumors. No rear rangements of the NF2 gene could be defected by Southern analysis of r estriction endonuclease-digested genomic DNA, and no abnormally migrat ing bands were detected on single strand conformation analysis of indi vidual exons of the NF2 gene. Thus, although frequent loss of heterozy gosity on chromosome 22 suggests that inactivation of a tumor suppress or gene an this chromosome plays a role in development of gliomas, the re is no evidence that inactivation of the NF2 gene is implicated in t his process, confirming the results of other studies of the NF2 gene i n human gliomas. The identity of the putative tumor suppressor gene on 22q involved in development of gliomas remains unknown. (C) Elsevier Science Inc., 1996