Oncomutations as Biomarkers of Cancer Risk

摘要: Cancer risk assessment impacts a range of societal needs, from the regulation chemicals to achieving best possible human health outcomes. Because oncogene and tumor suppressor gene mutations are necessary for development cancer, such ideal biomarkers use in cancer assessment. Consequently, DNA-based methods quantify particular tumor-associated hotspot point (i.e., oncomutations) have been developed, including allele-specific competitive blocker-PCR (ACB-PCR). Several studies using ACB-PCR model mutagens demonstrated that significant induction oncomutations measureable at earlier time points than used score tumors bioassay. In case benzo[a]pyrene K-Ras codon 12 TGT mutation A/J mouse lung, measurement oncomutation was shown be an more sensitive endpoint response. The by led two unexpected findings. First, present various tissues control rodents "normal" colonic mucosa samples relatively high frequencies. Approximately 60% (88/146) mutant fractions (MFs) >10(-5), some MFs as 10(-3) or 10(-4). Second, preliminary data indicate frequently subpopulations tumors. These findings integrated into hypothesis predominant preexisting may useful generic reporters carcinogenesis. Future research opportunities described, rodent extrapolation, dose-response assessment, personalized medicine.