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 chromosome arm 3p is a frequent event in upper aerodigestive tract squamous cell carcinoma (UADT SCC). Recently, the Von-Hippel Lindau (VHL) tumor suppressor gene was identified at chromosome band 3p25-26. To determine 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 shown to exhibit allelic loss of 3p were tested for LOH surrounding the VHL locus using four different polymorphic markers. All of the samples (100%) exhibited LOH for at least 1 marker. However, no LOH was detected using a polymorphism within exon 1 of the VHL gene which was informative for 18 of the 26 cases. Furthermore, mutations of the VHL gene could not be identified by single-strand conformation polymorphism, dideoxyfingerprint or direct DNA sequence analysis. In addition, the VHL gene was not inactivated by hypermethylation in any of the 26 tumor samples studied. These findings demonstrate that allelic loss of chromosome arm 3p in UADT SCC involves regions surrounding the VHL locus but does not include the VHL gene. The VHL gene, therefore, does not appear to be involved in the pathogenesis of UADT SCC.