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©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2026; 32(6): 116028
Published online Feb 14, 2026. doi: 10.3748/wjg.v32.i6.116028
Published online Feb 14, 2026. doi: 10.3748/wjg.v32.i6.116028
Emerging role of DNA polymerase epsilon non-exonuclease domain mutations in colorectal cancer: From sequence variants to clinical implications
Jia-Ju Xu, Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, China
Chun-Xiao Ni, Department of Minimally Invasive Oncology, Tai’an City Central Hospital, Tai’an 271000, Shandong Province, China
Jia-Ju Xu, Department of Medical Oncology, Tai’an City Central Hospital, Tai’an 271000, Shandong Province, China
Co-first authors: Jia-Ju Xu and Chun-Xiao Ni.
Author contributions: Xu JJ, Ni CX and Xu JJ (corresponding author) contributed to this paper; Xu JJ (corresponding author) was responsible for the manuscript’s intellectual direction, from the initial overall concept and outline to the specific discussion; Xu JJ and Ni CX contributed to the writing, editing the manuscript, and review of literature.
Supported by the Scientific Research Fund of Tai’an Science and Technology Agency, No. 2019NS180.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jia-Ju Xu, MD, Doctor, Department of Medical Oncology, Tai’an City Central Hospital, No. 29 Longtan Road, Tai’an 271000, Shandong Province, China.
Received: November 2, 2025
Revised: December 19, 2025
Accepted: December 25, 2025
Published online: February 14, 2026
Processing time: 94 Days and 0.7 Hours
Revised: December 19, 2025
Accepted: December 25, 2025
Published online: February 14, 2026
Processing time: 94 Days and 0.7 Hours
Core Tip
Core Tip: Building on Taskiran et al’s findings of a high frequency of non-exonuclease domain mutations (non-EDMs) in polymerase epsilon (POLE), particularly the p.V1446fs3 variant, this editorial highlights their potential clinical significance in colorectal cancer. These non-EDMs, often co-occurring with mutations in DNA repair and oncogenic signaling genes, may define a distinct subgroup of tumors. The editorial advocates for functional validation and the integration of comprehensive POLE sequencing into molecular subtyping to unlock their potential as biomarkers for guiding immunotherapy and personalized treatment strategies.