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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2025; 31(44): 112524
Published online Nov 28, 2025. doi: 10.3748/wjg.v31.i44.112524
Published online Nov 28, 2025. doi: 10.3748/wjg.v31.i44.112524
DNA polymerase epsilon-mutant colorectal cancers: Insights into non-exonuclease domain mutation variants, microsatellite instability status, and co-mutation profiles
Ismail Taskiran, Department of Gastroenterology, School of Medicine, Aydin Adnan Menderes University, Aydin 09010, Türkiye
Seda Orenay-Boyacioglu, Department of Medical Genetics, School of Medicine, Aydin Adnan Menderes University, Aydin 09010, Türkiye
Olcay Boyacioglu, Faculty of Engineering, Aydin Adnan Menderes University, Aydin 09010, Türkiye
Ibrahim Halil Erdogdu, Nil Culhaci, Ibrahim Meteoglu, Department of Pathology, School of Medicine, Aydin Adnan Menderes University, Aydin 09010, Türkiye
Author contributions: Taskiran I, Orenay-Boyacioglu S, Boyacioglu O, Erdogdu IH, Culhaci N and Meteoglu I conceptualized and designed the study; Orenay-Boyacioglu S, Boyacioglu O and Erdogdu IH performed the investigation and formal analysis; Taskiran I, Orenay-Boyacioglu S, Boyacioglu O, Erdogdu IH, Culhaci N and Meteoglu I contributed to methodology and project administration; Taskiran I provided resources; Taskiran I, Orenay-Boyacioglu S, Boyacioglu O, Erdogdu IH, Culhaci N and Meteoglu I supervised the work; Orenay-Boyacioglu S, Boyacioglu O and Erdogdu IH prepared the original draft; Taskiran I, Orenay-Boyacioglu S, Boyacioglu O, Erdogdu IH, Culhaci N and Meteoglu I reviewed and edited the manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: This study was approved by the Aydin Adnan Menderes University Non-Interventional Clinical Research Ethics Committee (2024/#138). The Helsinki Declaration criteria were also followed.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: All relevant data are included in the manuscript. Materials, data, and protocols described within the paper are available upon reasonable request to the corresponding author.
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: Olcay Boyacioglu, PhD, Associate Professor, Faculty of Engineering, Aydin Adnan Menderes University, Merkez Kampus, Efeler, Aydin 09010, Türkiye.
Received: July 30, 2025
Revised: September 13, 2025
Accepted: October 20, 2025
Published online: November 28, 2025
Processing time: 121 Days and 18.3 Hours
Revised: September 13, 2025
Accepted: October 20, 2025
Published online: November 28, 2025
Processing time: 121 Days and 18.3 Hours
Core Tip
Core Tip: This study highlights the overlooked role of DNA polymerase epsilon (POLE) non-exonuclease domain mutations in colorectal cancer. By integrating next-generation sequencing with microsatellite instability testing, we show that POLE mutations are frequent, particularly in microsatellite-low tumors, and are often accompanied by co-mutations in MLH3, MSH3, KRAS, PIK3CA, and BRAF. These findings extend beyond the classical exonuclease domain hotspots, suggesting that both exonuclease and non-exonuclease POLE variants may serve as valuable biomarkers for prognosis and support the development of personalized treatment strategies in colorectal cancer management.