Frequent adduct formation has occurred at guanine positions on codons 157, 158, 245, 248, and 273. These positions favor PAH adduct formation and are major mutational hotspots.  


G to T mutations in Lung Cancer are consistent with adduct spectrum and mutations of PAHs



For lung cancers, some of the specific mutational hotspots include codons 157,158,245,248, and 273 (mostly G to T mutations). 248 and 273 are the most common targets for the G to T transversions and are the most common for the entire p53 mutation database. When these are mutated, p53’s function is altered and aggregates p53’s ability to act as a transcription factor to activated other genes. 


State University of New York at Stony Brook

Carcinogens liken to target the tumor suppressor genes or oncogenes primarily. Mutations that occur on the p53 tumor suppressor gene are common in smokers and the lungs. An excess of G-to-T transversions occurs for these tumors that grow here. Around 30% of the point mutations that happen on this gene are the G-toT transversions (in smokers), as compared to 12% in non-smokers. Nonsmokers have an increased number of G to A transversions (47% to 27% smokers). 



Carcinogen Targets

Pfeifer, G. P., Denissenko, M. F., Olivier, M., Tretyakova, N., Hecht, S. S., & Hainaut, P. (2002). Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene, 21(48), 7435–7451. https://doi.org/10.1038/sj.onc.1205803

Tobacco Smoke Carcinogens Reference

P53 mutations do not occur randomly but have certain mutation hotspots. These hotspots are within a domain of about 180 amino acids from codon 120 to 130. These are specifically G-to-T transversions in lung cancer, brain, breast, and colorectal cancers. The hotspot locations are important because they can allow the specific assignment of particular carcinogens to that mutated site. These specific sites can also be linked to specific cancers.  


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