However, genomic events that are acquired during cancer progression tend to have lower relative VAF in ctDNA than do early truncal mutations, such as those in tumor suppressor genes or clonal RAS mutations.13 In our series, fusions occurring at low rVAF tended to be found in samples containing other genomic mechanisms of anti-EGFR therapy resistance, which is consistent with our hypothesis that some fusions in CRC occur at subclonal levels that are undetectable in pretreatment tissue but are selected for and become detectable in ctDNA after anti-EGFR therapy resistance. This evidence concerns the gene EGFR and colorectal carcinoma.