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), have been utilised to explore these context effects. BPDE is known to form an adduct at the guanines in a number of RAS gene sites, KRAS codons 12, 13 and 14, NRAS codon 12, and HRAS codons 12 and 14.

Results

Molecular modelling techniques, along with multivariate analysis, have been utilised to determine the sequence influenced differences between BPDE-adducted RAS gene sequences as well as the local distortion caused by the adducts.

Conclusions

We conclude that G:C > T:A mutations at KRAS codon 12 in the tumours of lung cancer patients (who smoke), proposed to be predominantly caused by BPD

SUBMITTER: Menzies GE 

PROVIDER: S-EPMC8439098 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature