Mutation of the von Hippel-Lindau tumour suppressor gene in capillary haemangioblastomas of the central nervous system

Abstract

A series of 20 capillary haemangioblastomas of the central nervous system was screened for mutations of the von Hippel-Lindau (VHL) tumour suppressor gene by single strand conformational polymorphism (SSCP) and heteroduplex analysis. Aberrant polymerase chain reaction (PCR) products were detected in ten tumours. DNA sequencing of these PCR products revealed that seven tumours had frameshift mutations due either to deletions of one or more base pairs (six cases) or to insertion of one base pair (one case). The remaining three tumours had either point mutations of intron splice site sequences (two cases) or a point mutation resulting in an amino acid substitution (one case). Evidence for germline alterations of the VHL gene was found in two patients who showed identical mutations in both tumour and corresponding leukocyte DNA. The results suggest that mutation of the VHL tumour suppressor gene represents a significant event in the development of capillary haemangioblastomas.