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.  


State University of New York at Stony Brook


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. 


Target codons for mutation

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

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