Two new tumor-suppressor genes, the cyclin dependent kinase 4 inhibitor gene (p16/CDKN2) and the von Hippel-Lindau disease gene (VHL), have been cloned and mapped on chromosomes 9p and 3p respectively, where putative tumor-suppressor genes of the oral squamous-cell carcinoma (SCC) may be present. In order to elucidate whether abnormalities of these genes could contribute to the tumorigenesis of oral SCC, genomic DNAs from 62 tissue samples of tumors (32 primary SCCs and 30 pre-cancerous lesions) and from 7 oral SCC cell lines were examined by polymerase chain reaction-single strand conformation polymorphism analysis and direct DNA sequencing. Four of 7 (57%) cell lines contained nonsense mutations or missense mutations in the p16/CDKN2 gene and 2 of 32 (6%) primary oral SCCs had nonsense mutations. Particularly, 3 of 4 nonsense mutations detected in the present study were found in codon 80 (CGA-->TGA; Arg-->Stop), suggesting that codon 80 was a mutational hot spot of the p16/CDKN2 gene. No VHL gene mutation was found in any subject. These results suggest that mutation of the VHL gene is not a common factor in the development of human oral SCC. In contrast, the p16/CDKN2 gene may be correlated with the progression of a subtype of this cancer.

Related Articles