DNA polymerase epsilon-mutant colorectal cancers: Insights into non-exonuclease domain mutation variants, microsatellite instability status, and co-mutation profiles

<i>POLE</i> mutations, especially non-EDMs, are frequent in MSI-L CRC and often co-occur with <i>MLH3, MSH3, KRAS, PIK3CA</i>, and <i>BRAF,</i> highlighting their potential role in tumor biology and as biomarkers for personalized treatment. Functional validation and multicenter studies are needed.