Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastroenterol. Aug 28, 2026; 32(32): 118014
Published online Aug 28, 2026. doi: 10.3748/wjg.118014
Published online Aug 28, 2026. doi: 10.3748/wjg.118014
Non-exonuclease domain POLE mutations and their biological significance in colorectal cancer
Ilektra Kyrochristou, Gerasimia D Kyrochristou, Georgios D Lianos, Department of General Surgery, University Hospital of Ioannina, Ioannina 45500, Greece
Author contributions: Kyrochristou I contributed to the original draft; Lianos G contributed to the conceptualization; Kyrochristou GD contributed to the writing; Kyrochristou I and Lianos GD contributed to the review and editing; All authors have read and approved the final version of the manuscript.
AI contribution statement: The AI tools ChatGPT 5.2 have been used to correct language and expression mistakes.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Corresponding author: Ilektra Kyrochristou, Department of General Surgery, University Hospital of Ioannina, Stavros Niarchos Avenue, Ioannina 45500, Greece.
Received: January 5, 2026
Revised: February 10, 2026
Accepted: May 18, 2026
Published online: August 28, 2026
Processing time: 223 Days and 12.1 Hours
Revised: February 10, 2026
Accepted: May 18, 2026
Published online: August 28, 2026
Processing time: 223 Days and 12.1 Hours
Core Tip
Core Tip: Non-exonuclease domain (EDM) DNA polymerase epsilon (POLE) mutations represent an emerging molecular subgroup in colorectal cancer. Particularly in microsatellite stable tumors, these variants co-occur with elevated mutational burden, altered DNA repair, and co-mutational profiles (KRAS, phosphatidylinositol 3-kinase catalytic subunit alpha, MutL homolog 3, and MutS homolog 3). Rather than acting as isolated biomarkers, non-EDM POLE mutations appear to influence tumor biology through their broader genomic context, highlighting the need for comprehensive biomarker models instead of relying solely on traditional mismatch repair status.