This observation, coupled with the fact that PAX6 mutations were more frequent among late-stage than early-stage MSI-hypermutated tumors (25.9% versus 3.5%, respectively), raise the possibility that, like KLF3 mutations, PAX6 mutations may be pathogenic drivers of tumor progression in the context of MSI-hypermutated EECs. This evidence concerns the gene KLF3 and neoplasm.