Abstract

Background and Objectives: Telomere regulation have an association with colorectal cancer. Previous studies demonstrated its implication in colorectal carcinogenesis. This study aimed to identify the role of telomerase reverse transcriptase (TERT) in colorectal carcinogenesis and determine TERT expression and their associated genes in precancerous lesions. Materials and Methods: TERT expression in 93 colorectal precursor lesions was analyzed. This included 61 tubular adenomas (TAs) and 32 serrated polyps (SPs). Furthermore, KRAS and BRAF gene mutations and microsatellite instability were analyzed. Statistical tests were performed to analyze the relationship between variables. Results: TERT expression in TAs, when compared with those observed in paired adjacent nontumor tissues, was 0.92 ± 0.78. TERT expression levels were significantly lower in SPs (0.38 ± 0.14, p < 0.001). KRAS and BRAF mutations were mutually exclusive in TAs and SPs (p < 0.001). TERT expression tended to be associated with KRAS mutations (46.7% vs. 22.0%, p = 0.098) and low-grade tumors (35.0% vs. 16.0%, p = 0.096), but this difference was insignificant. Conclusions: TERT expression has a pivotal role in progression to TAs in colorectal tissue. Considering the association between TERT expression and KRAS mutation, therapeutic drugs targeting this pathway can be developed for cancer prevention.

Highlights

  • The majority of colorectal cancers (CRC) are developed from the adenoma–carcinoma series caused by the sequential accumulation of genetic alterations [1]

  • KRAS and BRAF mutations were mutually exclusive in tubular adenomas (TAs) and serrated polyps (SPs) (p < 0.001)

  • telomerase reverse transcriptase (TERT) expression tended to be associated with KRAS mutations (46.7% vs. 22.0%, p = 0.098) and low-grade tumors

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Summary

Introduction

The majority of colorectal cancers (CRC) are developed from the adenoma–carcinoma series caused by the sequential accumulation of genetic alterations [1]. Tubular adenomas (TAs) are associated with APC, KRAS, and p53 mutations, while serrated polyps (SPs) progress through microsatellite instability (MSI) and BRAF mutations [2,3,4]. Telomere length becomes critically short inducing replicative senescence and apoptosis [6]. Telomere regulation have an association with colorectal cancer. This study aimed to identify the role of telomerase reverse transcriptase (TERT) in colorectal carcinogenesis and determine TERT expression and their associated genes in precancerous lesions. Materials and Methods: TERT expression in 93 colorectal precursor lesions was analyzed. This included 61 tubular adenomas (TAs) and 32 serrated polyps (SPs). KRAS and BRAF gene mutations and microsatellite instability were analyzed. Statistical tests were performed to analyze the relationship between variables

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