The responses to both chemotherapy and targeted therapy were not durable and this may be due to the known aggressiveness of MSI-stable BRAF-mutant colon cancers, especially those that, like in this patient, do not harbor RNF43 mutations.21 Very high BRAF variant allele frequencies in plasma were also noted at progression, which is also associated with aggressive disease.22 This evidence concerns the gene BRAF and malignant colon neoplasm.