ANALYSIS OF THE NF2 TUMOR-SUPPRESSOR GENE AND OF CHROMOSOME-22 DELETIONS IN GLIOMAS

Recurrent deletions of chromosome fragments observed in neoplasms are thought to participate in tumor development through the inactivation o f tumor-suppressor genes. In gliomas, the most frequent deletions invo lve chromosome arms 9p, 10q, 17p, 19q and 22q. We have analysed deleti ons of chromosome 22 in gliomas by studying loss of heterozygosity (LO H) at 8 microsatellite loci. LOH for this chromosome fragment was obse rved in 17/70 (24%) cases, most of them encompassing the region which encodes the gene altered in neurofibromatosis 2 (NF2), an inherited di sease which predisposes to tumors of the nervous system. To investigat e the possible involvement of the NF2 tumor-suppressor gene in the tum origenesis of gliomas, we searched for alterations in its genomic stru cture and in its mature transcript. Northern-blot and reverse transcri ptase-PCR experiments showed that the NF2 transcript is expressed and does not demonstrate obvious structural alterations. Moreover, analysi s, at the genomic level, of the 16 coding exons of the NF2 gene by den aturing gradient gel electrophoresis failed to detect any somatically acquired point mutations. Altogether, these data strongly suggest that , although gliomas demonstrate recurrent chromosome 22 deletions most frequently encompassing the NF2 region, the NF2 gene is not altered in these tumors. (C) 1995 Wiley-Liss, Inc.