Von Hippel-Lindau tumour suppressor gene is not involved in sporadic human breast cancer.

Mutations of the von Hippel-Lindau (vhl) gene, as well as allelic loss at the gene region (3p25-26) have been described in sporadic cases of the tumour types participating in VHL disease, but also in cancers not associated with the syndrome. In this study, we attempted mutation analysis of the vhl gene, as well as detection of allelic loss at 3p25-26 in sporadic human breast cancer. Eighty-two tumour specimens were screened for loss of heterozygosity (LOH) at the vhl region, and compared to the adjacent, histologically normal tissue. Furthermore, mutations within the three exons of vhl in the same panel of tumours were detected using SSCP and heteroduplex analysis and direct sequencing. To our knowledge this is the first mutational analysis reported for the vhl gene in breast cancer, however we failed to reveal any mutations in the specimens examined. All the cases were informative for at least one of the microsatellite markers tested, 24 (29.2%) exhibited LOH at 3p25-26. Clinical and pathological data were available for all tumours examined, however no significant correlations were encountered. These results strongly indicate against a critical involvement of the tumour suppressor vhl in breast carcinogenesis.