FREQUENT ALLELIC LOSS AT CHROMOSOME ARM 3P IS DISTINCT FROM GENETIC ALTERATIONS OF THE VON-HIPPEL LINDAU TUMOR-SUPPRESSOR GENE IN HEAD AND NECK-CANCER

Previous molecular genetic studies revealed that allelic loss of chrom osome arm 3p is a frequent event in upper aerodigestive tract squamous cell carcinoma (UADT SCC), Recently, the Von-Hippel Lindau (VHL) tumo r suppressor gene was identified at chromosome band 3p25-26. To determ ine if the VHL locus is altered in these tumors, a paired series of 26 tumors and blood from patients with UADT SCC that were previously sho wn to exhibit allelic loss of 3p were tested for LOH surrounding the V HL locus using four different polymorphic markers, All of the samples (100%) exhibited LOH for at least 1 marker, However, no LOH was detect ed using a polymorphism within exon 1 of the VHL gene which was inform ative for 18 of the 26 cases, Furthermore, mutations of the VHL gene c ould not be identified by single-strand conformation polymorphism, did eoxyfingerprint or direct DNA sequence analysis, In addition, the VHL gene was not inactivated by hypermethylation in any of the 26 tumor sa mples studied, These findings demonstrate that allelic loss of chromos ome arm 3p in UADT SCC involves regions surrounding the VHL locus but does not include the VHL gene, The VHL gene, therefore, does not appea r to be involved in the pathogenesis of UADT SCC.