Selective loss of resistant alleles at p15INK4B and p16INK4A genes in chemically-induced rat tongue cancers

We previously reported that susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancer in Dark-Agouti (DA) and Wistar/Furth (WF) rats was determined by a number of quantitative trait loci. In this article, we further scrutinized one of the quantitative trait loci at a suggestive level on rat chromosome 5. Analyzing a DNA panel of 130 (DA × WF) F2 rats treated with 4NQO showed a quantitative trait loci, containing p15INK4B and p16INK4A. To study the possible relevance of these genes in the development of tongue cancer, we examined 45 4NQO-induced tongue cancers in 100 (DA × WF) F1 rats for loss of heterozygosity. The incidence of loss of heterozygosity at p15INK4B and p16INK4A genes in large advanced tongue cancers was 37.8% and 40.0%, respectively, and the WF allele was selectively lost. Accumulation of loss of heterozygosity and methylation of the promoter regions in the tumour suppressor genes in advanced tumours suggests that they may play a role in tongue cancer progression.