Absence of TERT promoter mutations in colorectal precursor lesions and cancer

Cruvinel-Carloni, Adriana; Yamane, Letícia; Scapulatempo‐Neto, Cristovam; Guimarães, Denise Peixoto; Reis, Rui Manuel

doi:10.1590/1678-4685-gmb-2017-0133

Cited by 4 publications

(3 citation statements)

References 16 publications

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“…We investigated whether samples in our cohort also harbored somatic mutations at chr5: 1, 295, 228 and chr5: 1, 295, 250 within the TERT promoter, but we found that none of our cancer samples carried these mutations (see Mendeley data). The TERT promoter was also devoid of any somatic single-nucleotide or indel mutations, confirming previous reports that such mutations are of low frequency in colorectal cancer (24,25).…”

Section: Resultssupporting

confidence: 88%

Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing

Poulos

Perera

Packham

et al. 2019

JNCI Cancer Spectrum

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Background Genetic testing of cancer samples primarily focuses on protein-coding regions, despite most mutations arising in noncoding DNA. Noncoding mutations can be pathogenic if they disrupt gene regulation, but the benefits of assessing promoter mutations in driver genes by panel testing has not yet been established. This is especially the case in colorectal cancer, for which few putative driver variants at regulatory elements have been reported. Methods We designed a unique target capture sequencing panel of 39 colorectal cancer driver genes and their promoters, together with more than 35 megabases of regulatory elements focusing on gene promoters. Using this panel, we sequenced 95 colorectal cancer and matched normal samples at high depth, averaging 170× and 82× coverage, respectively. Results Our target capture sequencing design enabled improved coverage and variant detection across captured regions. We found cases with hereditary defects in mismatch and base excision repair due to deleterious germline coding variants, and we identified mutational spectra consistent with these repair deficiencies. Focusing on gene promoters and other regulatory regions, we found little evidence for base or region-specific recurrence of functional somatic mutations. Promoter elements, including TERT, harbored few mutations, with none showing strong functional evidence. Recurrent regulatory mutations were rare in our sequenced regions in colorectal cancer, though we highlight some candidate mutations for future functional studies. Conclusions Our study supports recent findings that regulatory driver mutations are rare in many cancer types and suggests that the inclusion of promoter regions into cancer panel testing is currently likely to have limited clinical utility in colorectal cancer.

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Section: Resultssupporting

confidence: 88%

Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing

Poulos

Perera

Packham

et al. 2019

JNCI Cancer Spectrum

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“…18 Similarly, these mutations were also not found in Brazilian CRC patients. 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.…”

Section: Discussionmentioning

confidence: 96%

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

Gurer¹,

DOORI²

2022

J Oncol Sci

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Telomerase reverse transcriptase (TERT) is one of the catalytic subunits of the telomerase enzyme involved in the lengthening of telomeres during cell division. Two hotspot mutations in the promoter region of the TERT gene, C228T and C250T have been observed in many different types of cancer. Besides, a limited number of available studies are related to colorectal cancer. However, no study to date has analyzed these mutations in the Turkish population. Hence, this study aimed to determine the frequency of C228T and C250T hotspot mutations in Turkish patients with colorectal cancer. Material and Methods: Tumors and adjacent healthy tissues of 43 colorectal cancer patients were analyzed in the study material. After genomic DNA extraction, 163 bp DNA fragment of the TERT promoter region was amplified by polymerase chain reaction (PCR) method. PCR products were sequenced using the bi-directional Sanger technique and a wildtype TERT promoter sequence obtained from the National Center for Biotechnology Information database was used for the comparison and detection of mutations. Results: Sequence analysis revealed no mutations in the promoter region of the TERT gene in colorectal cancer tissues or in healthy tissues. Conclusion: These findings of the study suggest that colorectal cancer in the Turkish population is not associated with the TERT promoter C228T and C250T hotspot mutations.

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“…Therefore, identifying genetic alterations in precursor lesions can lead to molecular-based strategies, improving the sensitivity, specificity, and impact of colorectal screening and surveillance programs. Nevertheless, few studies evaluated the mutation status in South America CRC precursor lesions [ 22 , 23 ]. Results of the first two years (first round) of our colorectal cancer screening program (from Barretos Cancer Hospital program) in Brazil showed a successful implementation with a high test return participation rate, colonoscopy completion, and detection lesion rates.…”

Section: Introductionmentioning

confidence: 99%

Somatic targeted mutation profiling of colorectal cancer precursor lesions

et al. 2022

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Background Most colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population. Methods In total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes. The genetic ancestry of the patients was estimated. Results Somatic driver mutations were identified in 66.7% of cases, including alterations in APC (32.2%), TP53 (20.0%), KRAS (18.9%), BRAF (13.3%) and EGFR (7.8%). Adenomas displayed a higher number of mutations, mainly in APC, compared to serrated polyps (73.1% vs. 47.8%, p = 0.026). Advanced adenomas had a significantly higher frequency of mutation in KRAS and a high overall mutation rate than early adenomas (92.9% vs. 59%, p = 0.006). A high degree of ancestry admixture was observed in the population studied, with a predominance of European components (mean of 73%) followed by African (mean of 11.3%). No association between genetic ancestry and type of lesions was found. The mutation profile of Brazilian colorectal precursor lesions exhibits alteration in APC, KRAS, TP53, and BRAF at different frequencies according to lesion type. Conclusions These results bestow the knowledge of CRC's biologic history and support the potential of these biomarkers for precursor lesions detection in CRC screening of the Brazilian population.

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Absence of TERT promoter mutations in colorectal precursor lesions and cancer

Cited by 4 publications

References 16 publications

Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing

Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing

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

Somatic targeted mutation profiling of colorectal cancer precursor lesions

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