Carcinogen-induced DNA structural distortion differences in the RAS gene isoforms; the importance of local sequence

Abstract Background Local sequence context is known to have an impact on the mutational pattern seen in cancer. The RAS genes and a smoking carcinogen, Benzo[a]pyrene diol epoxide (BPDE), been utilised explore these effects. BPDE form adduct at guanines number of gene sites, KRAS codons 12, 13 14, NRAS codon HRAS 12 14. Results Molecular modelling techniques, along with multivariate analysis, determine influenced differences between BPDE-adducted sequences as well local distortion caused by adducts. Conclusions We conclude that G:C > T:A mutations tumours lung cancer patients (who smoke), proposed be predominantly BPDE, are due effect interaction methyl group C5 position thymine base carcinogen investigated causing increased distortion. further suggest methylated cytosine would similar effect, showing importance methylation development.