SOMATIC MUTATIONS OF THE VON-HIPPEL-LINDAU TUMOR-SUPPRESSOR GENE AND LOSS OF HETEROZYGOSITY ON CHROMOSOME 3P IN HUMAN GLIAL TUMORS

Molecular genetic analysis of von Hippel-Lindau tumor suppressor gene (VHL gene) was performed on 38 tissues of human glial tumors (ependymo ma, 1; astrocytoma, 6; oligodendroglioma, 1; oligoastrocytoma, 2; anap lastic oligoastrocytoma, 3; anaplastic astrocytoma, 14; glioblastoma m ultiforme, 11), Somatic DNAs extracted from frozen tumor specimens wer e examined by single-strand conformational polymorphism analysis and d irect sequencing, In addition, Loss of heterozygosity (LOH) on chromos ome 3p in 15 glial tumor cases, lymphocyte DNAs of which were availabl e, was examined by use of 10 microsatellite probes and two polymorphis m markers for the VHL gene, Two cases of low-grade gliomas showed soma tic sense mutations in exon 3 of the VHL gene, and 6 of 15 cases (40.0 %) showed LOH of chromosome 3p. The VHL gene-mutated cases also showed LOH. The retention of heterozygosity and high pathological grade of g lial tumors were correlated significantly, In addition, Kaplan-Meier s urvival analysis for patients with glial tumors showed that patients w ith LOH had a significantly longer survival time than those without LO H, These results suggest that somatic mutations on 3p, including the V HL gene, may be involved in tumorigenesis of some low-grade glial tumo rs.