Tissue and Sex-Specific Performance of a Cancer Driver Based Biomarker in rasH2 Mice
Measurement of mutation levels as mutant fraction (MF) in normal tissues by CarcSeq, with statistical analysis based on median absolute deviation (MAD) in MF, is being developed as an approach to assess clonal expansion of cancer driver gene mutants. If validated, this approach could contribute to weight of evidence-based carcinogenicity assessment and enable the evaluation of the carcinogenic potential in rodents before the appearance of histological lesions. This study leveraged the sex-related difference in lung tumor development for the rasH2 mouse model to evaluate different analytical approaches for quantifying clonal expansion, specifically the best approach for selecting tissue specific cancer driver gene targets and identifying the appropriate median for calculating MAD in MF.