In order to investigate the clinical usefulness of these mutations in lung cancer, we applied a sensitive method to compare mutations in codon 12 of the K-ras gene in DNA extracted from lung tumours and the matched sputum samples obtained from 22 lung cancer patients.
Primer extension assays with purified BALB/cJ and A/J proteins in vitro demonstrate that both forms of Pol iota are active but that they may differ in substrate discrimination, which may affect the formation of Kras2 mutations in mouse lung tumors.
Further studies on these potential regulatory sites may help to elucidate the fundamental mechanism underlying allele-specific activation and expression of K-ras gene in hybrid mouse lung tumors, which determines lung tumor susceptibility in mice.
In this study, TP53 (exons 5-9) and KRAS (codon 12) were analyzed in primary lung tumors of never (n = 40), former (n = 27), and current smokers (n = 64; mainly heavy smokers).
The incidence of KRAS2 mutations in human compared to mouse lung tumors differed significantly, as did the incidence of Hras and p53 gene mutations in human compared to mouse liver tumors.
The incidence of KRAS2 mutations in human compared to mouse lung tumors differed significantly, as did the incidence of Hras and p53 gene mutations in human compared to mouse liver tumors.
We propose that the Pas1 modifier effect is due to Kras2, and that a sensitive balance between the expression levels of wild-type and mutant alleles determines lung tumor susceptibility.
K-ras mutations in lung tumors and tumors from other organs are consistent with a common mechanism of ethylene oxide tumorigenesis in the B6C3F1 mouse.