SOMATIC MUTATIONS OF THE VON HIPPEL-LINDAU TUMOR-SUPPRESSOR GENE IN SPORADIC CENTRAL-NERVOUS-SYSTEM HEMANGIOBLASTOMAS

Hemangioblastoma is one of the benign tumors in the central nervous sy stem. It is often associated with the von Hippel-Lindau (VHL) disease, a well known hereditary tumor syndrome. It is believed that inactivat ion of both alleles of VHL tumor suppressor gene is essential in the t umorigenic processes in hemangioblastomas associated with VHL disease. The molecular basis for the development of sporadic hemangioblastomas is not known. Here, we analyzed 13 cases of primary sporadic hemangio blastomas for somatic mutations of VHL gene with single strand conform ational polymorphism analyses of the tumor DNAs. We detected abnormal single strand conformational polymorphism pattern in 7 tumors (54%). O f these 7 possibly mutated tumors, we successfully characterized 3 tum ors by direct sequencing. We were unable to sequence 4 tumors because of the poor quality of DNA obtained from paraffin blocks. Somatic muta tions in the 3 tumors were 2 missense mutations and 1 microdeletion. T hese mutations were observed in 1 tumor in exon 1 and 2 tumors in exon 2. Our results suggest that mutations of VHL tumor suppressor gene ar e involved in the development of at least 20% of sporadic central nerv ous system hemangioblastomas.