AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025140085
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ORIGINAL RESEARCH ARTICLE

Exploring genetic and epigenetic alterations in hTERT gene in colorectal cancer

Meryem Jafari1,2,3 ,  Boutaina Addoum2* ,  Abdelilah Laraqui3 ,  Mohammed Oukabli4 ,  Ahmed Bounaim5 ,  Abdelmounim Ait Ali5 ,  Sidi Mohammed Bouchantouf5 ,  Noureddine Njoumi5 ,  Belkouchi Abdelkader6 ,  Fatima Zohra BenMoula6 ,  Hicham El Annaz3 ,  Khalid Ennibi3 ,  Imane Chaoui2 ,  Youssef Bakri1 ,  Mohammed Attaleb2
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1 Laboratory of Biology and Human Pathologies, Genomic Center of Human Pathologies, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco
2 Biology and Medical Research Unit, National Center for Nuclear Energy, Sciences and Techniques, Rabat, Morocco
3 Clinical and Epidemiological Research Unit, Center of Virology, Infectious and Tropical Diseases, Mohammed V Military Teaching Hospital, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
4 Department of Pathology, Mohammed V Military Teaching Hospital of Rabat, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco
5 Department of Digestive Surgery, Faculty of Medicine and Pharmacy, Mohammed V Military Hospital, Mohammed V University of Rabat, Rabat, Morocco
6 Department of Surgery, Ibn Sina Hospital, Rabat, Morocco
EJMO, 025140085 https://doi.org/10.36922/EJMO025140085
Received: 2 April 2025 | Revised: 22 April 2025 | Accepted: 13 May 2025 | Published online: 3 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Colorectal cancer (CRC) is a heterogeneous and multifactorial malignancy driven by a series of genetic and epigenetic alterations. In this field, telomere/telomerase dysfunction contributes to CRC carcinogenesis by impairing genomic stability and cellular replication. Objective: This study aimed to evaluate genetic and epigenetic alterations in CRC by examining mutation rates in the human telomerase reverse transcriptase (hTERT) promoter region, relative telomere length (RTL), hTERT gene expression, and DNA methylation in the TERT hypermethylated oncological region (THOR). Methods: A total of 45 CRC and 34 adjacent normal tissue samples from Moroccan patients were analyzed using molecular approaches, such as Sanger sequencing, quantitative PCR (qPCR), reverse transcription qPCR (RT-qPCR), and methylation-specific PCR (MSP). Results: No mutations in the hTERT promoter region were identified. However, hypermethylation in the THOR region was reported in 82.2% of CRC samples and 79.4% of adjacent normal tissues. High hTERT expression was detected in 50% of CRC patients. In addition, telomere length was significantly shorter (p=0.002) in cancerous tissues (1.41 [1.36 – 1.43]) compared to normal mucosa (1.559 [1.46 – 1.63]), with an RTL ratio less than 1 (0.90 [0.86 – 0.95]). No significant differences were found between clinicopathological features and hTERT expression, THOR methylation, or RTL, except for a significant correlation between THOR hypermethylation and smaller tumor size (p=0.017) and between THOR methylation and RTL in CRC tissues (p=0.034). Conclusion: These results suggest that telomere lengthening is crucial for CRC initiation and progression, and cancer cells tend to shorten telomeres to maintain the chromosomal instability (CIN) required for tumor progression. Further research is needed to elucidate the mechanisms underlying telomere shortening in CRC and understand the role of telomerase/telomere complex in CRC initiation and progression, which could provide new diagnostic, prognostic, and therapeutic targets.

Keywords
Colorectal cancer
THOR methylation
hTERT promoter mutation
Gene expression
Telomere length
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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