MUTATION OF THE VON HIPPEL-LINDAU TUMOR-SUPPRESSOR GENE IN CAPILLARY HEMANGIOBLASTOMAS OF THE CENTRAL-NERVOUS-SYSTEM

A series of 20 capillary haemangioblastomas of the central nervous sys tem was screened for mutations of the von Hippel-Lindau (VHL) tumour s uppressor gene by single strand conformational polymorphism (SSCP) and heteroduplex analysis, Aberrant polymerase chain reaction (PCR) produ cts were detected in ten tumours, DNA sequencing of these PCR products revealed that seven tumours had frameshift mutations due either to de letions of one or more base pairs (six cases) or to insertion of one b ase pair (one case), The remaining three tumours had either point muta tions of intron splice site sequences (two cases) or a point mutation resulting in an amino acid substitution (one case), Evidence for germl ine alterations of the VHL gene was found in two patients who showed i dentical mutations in both tumour and corresponding leukocyte DNA, The results suggest that mutation of the VHL tumour suppressor gene repre sents a significant event in the development of capillary haemangiobla stomas.