Different TERT Expression between Colorectal Adenoma and Serrated Polyp

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.

Lack of Telomerase Reverse Transcriptase Promoter C228T and C250T Hotspot Mutations in Colorectal Cancer Patients in Türkiye

“…4,8 Previous studies have shown that the telomerase activity plays an important role in the prognosis of CRC. 7 Both C228T and C250T mutations, identified in the TERT promoter region, cause the formation of a new binding site for E-twenty-six transcription factors and thereby increases the expression level of the TERT gene. 5,31 Hotspot mutations in the promoter region of the TERT gene were first identified in melanomas but were also frequently seen in various other tumors.…”

“…32 Besides, TERT promoter mutations were also not found in pheochromocytoma, gastrointestinal and kidney tumors, gastric cancer, colorectal precursor lesions, including tubular adenomas and serrated polyps. 7,33,34 On the other hand, Siraj et al reported TERT promoter mutations, -124C>T and -146C>T, in 13 different cancer types seen in Middle Eastern countries. They reported that TERT promoter mutations were most frequently detected in the 68.6% of bladder cancer, followed by 15.4% of thyroid cancer, 28.7% of nervous system tumors, 9.3% of prostate cancer, 3.7% of endometrial carcinoma, 1.4% of rhabdomyosarcoma, 1% of CRC, and 0.7% of breast cancer cases.…”

“…This telomere shortening causes aging or senescence and eventually cell death. 7,8 There are different approaches being explored to prevent telomere shortening; one of them is the upregulation of the telomerase gene. 9,10 Telomerase, a ribonucleoprotein complex composed of telomerase reverse transcriptase (TERT) protein and telomerase RNA component, loses efficiency in many somatic cells but has been found to be active in almost 80-90% of human carcinomas.…”

The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region

“…Telomerase reverse transcriptase (TERT), as the core component of telomerase regulation, is closely related to the development of cancer and cell growth [5]. Significantly elevated expression levels of human TERT (hTERT) have been found in most human malignancies, such as sarcomas [6], brain tumors [7], colorectal tumors [8], and breast cancer [9], increasing the risk of tumor recurrence. Studies have shown that mutations and methylation in the hTERT promoter region play a crucial role in the regulation of hTERT transcription levels and telomerase activity [10][11][12][13].…”

Chinese consensus on prevention of colorectal neoplasia (2021, Shanghai)

“…Patients with serrated polyposis syndrome and their pedigree members are recommended to undergo regular colonoscopic surveillance and immediate removal of the polyps Level of evidence: III Grade of recommendation: B Approval rate: 97.5%Serrated polyposis syndrome is a genetic disease characterized by multiple serrated polyps in the colorectum 280. The World Health Organization (WHO) recommends serrated polyposis syndrome to be diagnosed when meeting any of the following criteria: (a) ≥5 serrated lesions/polyps proximal to the rectum, all are ≥5 mm in size, of which at least two polyps are ≥10 mm; (b) at least 20 serrated lesions/polyps in any size distributed throughout the large bowel, of which ≥5 polyps are proximal to the proximal rectum 281.…”