Therefore, whereas P286R and WT POLE samples were likely classified as MSI-L due to chance mutation of a locus assayed in the Bethesda test, the V411L POLE samples might actually represent bona fide MMR-deficient (i.e., MSI-H) cases that were misclassified as MSI-L by the Bethesda assay, which was developed and validated in colon tumor cohorts (in which concurrent POLE/POLD1 proofreading loss and MSI has not been observed). This evidence concerns the gene POLD1 and colonic neoplasm.