TERT promoter hotspot mutations and their relationship with TERT levels and telomere erosion in patients with head and neck squamous cell carcinoma
Purpose To evaluate the prevalence of two recurrent somatic mutations (−124 C>T and −146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase ( TERT ) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous...
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| Published in: | Journal of cancer research and clinical oncology Vol. 146; no. 2; pp. 381 - 389 |
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| Main Authors: | , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Berlin/Heidelberg
Springer Berlin Heidelberg
01.02.2020
Springer Nature B.V |
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| ISSN: | 0171-5216, 1432-1335, 1432-1335 |
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| Abstract | Purpose
To evaluate the prevalence of two recurrent somatic mutations (−124 C>T and −146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase (
TERT
) as well as their relationship with
TERT
level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs).
Methods
We evaluate the prevalence of
TERT
promoter mutations,
TERT
levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs.
Results
Cancer tissue and AM specimens from 105 patients were analyzed
.
Telomere length and
TERT
mRNA levels were estimated using real-time polymerase chain reaction.
TERT
promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis.
TERT
promoter harbored mutations in 12 tumors (11.9%), with −124 C>T and −146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of
TERT
promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying
TERT
promoter mutations than in patients with unmutated
TERT
promoter cancers (
p
= 0.023).
TERT
levels in tumor did not significantly differ according to the mutational status of
TERT
promoter. No significant association was found between
TERT
promoter status and overall survival.
Conclusion
TERT
promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC.
TERT
levels, but not
TERT
promoter mutational status impact clinical outcome. |
|---|---|
| AbstractList | PurposeTo evaluate the prevalence of two recurrent somatic mutations (−124 C>T and −146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase (TERT) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs).MethodsWe evaluate the prevalence of TERT promoter mutations, TERT levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs.ResultsCancer tissue and AM specimens from 105 patients were analyzed. Telomere length and TERT mRNA levels were estimated using real-time polymerase chain reaction. TERT promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis. TERT promoter harbored mutations in 12 tumors (11.9%), with −124 C>T and −146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of TERT promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying TERT promoter mutations than in patients with unmutated TERT promoter cancers (p = 0.023). TERT levels in tumor did not significantly differ according to the mutational status of TERT promoter. No significant association was found between TERT promoter status and overall survival.ConclusionTERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC. TERT levels, but not TERT promoter mutational status impact clinical outcome. Purpose To evaluate the prevalence of two recurrent somatic mutations (−124 C>T and −146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase ( TERT ) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs). Methods We evaluate the prevalence of TERT promoter mutations, TERT levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs. Results Cancer tissue and AM specimens from 105 patients were analyzed . Telomere length and TERT mRNA levels were estimated using real-time polymerase chain reaction. TERT promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis. TERT promoter harbored mutations in 12 tumors (11.9%), with −124 C>T and −146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of TERT promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying TERT promoter mutations than in patients with unmutated TERT promoter cancers ( p = 0.023). TERT levels in tumor did not significantly differ according to the mutational status of TERT promoter. No significant association was found between TERT promoter status and overall survival. Conclusion TERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC. TERT levels, but not TERT promoter mutational status impact clinical outcome. To evaluate the prevalence of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase (TERT) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs). We evaluate the prevalence of TERT promoter mutations, TERT levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs. Cancer tissue and AM specimens from 105 patients were analyzed. Telomere length and TERT mRNA levels were estimated using real-time polymerase chain reaction. TERT promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis. TERT promoter harbored mutations in 12 tumors (11.9%), with -124 C>T and -146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of TERT promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying TERT promoter mutations than in patients with unmutated TERT promoter cancers (p = 0.023). TERT levels in tumor did not significantly differ according to the mutational status of TERT promoter. No significant association was found between TERT promoter status and overall survival. TERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC. TERT levels, but not TERT promoter mutational status impact clinical outcome. To evaluate the prevalence of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase (TERT) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs).PURPOSETo evaluate the prevalence of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase (TERT) as well as their relationship with TERT level, telomeres length, and outcome in patients with head and neck squamous cell carcinomas (HNSCCs).We evaluate the prevalence of TERT promoter mutations, TERT levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs.METHODSWe evaluate the prevalence of TERT promoter mutations, TERT levels, and telomere length in paired cancer tissue and adjacent mucosa (AM) in a series of HNSCCs.Cancer tissue and AM specimens from 105 patients were analyzed. Telomere length and TERT mRNA levels were estimated using real-time polymerase chain reaction. TERT promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis. TERT promoter harbored mutations in 12 tumors (11.9%), with -124 C>T and -146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of TERT promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying TERT promoter mutations than in patients with unmutated TERT promoter cancers (p = 0.023). TERT levels in tumor did not significantly differ according to the mutational status of TERT promoter. No significant association was found between TERT promoter status and overall survival.RESULTSCancer tissue and AM specimens from 105 patients were analyzed. Telomere length and TERT mRNA levels were estimated using real-time polymerase chain reaction. TERT promoter mutations were assessed using Sanger sequencing. Out of 105 cases, 101 were considered suitable for the analysis. TERT promoter harbored mutations in 12 tumors (11.9%), with -124 C>T and -146 C>T accounting for 83.3% and 16.7% of the alterations, respectively. No mutations were detected in AM samples. The prevalence of TERT promoter mutations was significantly higher in oral cavity SCCs (10 out of 27 tumors; 37%), and telomere length in AM was shorter in patients with tumors carrying TERT promoter mutations than in patients with unmutated TERT promoter cancers (p = 0.023). TERT levels in tumor did not significantly differ according to the mutational status of TERT promoter. No significant association was found between TERT promoter status and overall survival.TERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC. TERT levels, but not TERT promoter mutational status impact clinical outcome.CONCLUSIONTERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC. TERT levels, but not TERT promoter mutational status impact clinical outcome. |
| Author | Rampazzo, Enrica Boscolo-Rizzo, Paolo Mantovani, Monica Del Mistro, Annarosa Niero, Monia De Rossi, Anita Brutti, Martina Stellin, Marco Giunco, Silvia Spinato, Giacomo Rossi, Marco Guerriero, Angela Dei Tos, Angelo Paolo Tirelli, Giancarlo Bandolin, Luigia Menegaldo, Anna Da Mosto, Maria Cristina Polesel, Jerry |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31960186$$D View this record in MEDLINE/PubMed |
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| Copyright | Springer-Verlag GmbH Germany, part of Springer Nature 2020 Journal of Cancer Research and Clinical Oncology is a copyright of Springer, (2020). All Rights Reserved. Copyright Springer Nature B.V. Feb 2020 Springer-Verlag GmbH Germany, part of Springer Nature 2020 2020 |
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| Keywords | Promoter Head and neck squamous cell carcinoma Telomerase reverse transcriptase Mutation Telomere |
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To evaluate the prevalence of two recurrent somatic mutations (−124 C>T and −146 C>T) within the promoter of the gene encoding telomerase reverse... To evaluate the prevalence of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase... PurposeTo evaluate the prevalence of two recurrent somatic mutations (−124 C>T and −146 C>T) within the promoter of the gene encoding telomerase reverse... To evaluate the prevalence of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of the gene encoding telomerase reverse transcriptase... |
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| SubjectTerms | Adult Aged Aged, 80 and over Cancer Research Cohort Studies Female Head & neck cancer Head and neck carcinoma Head and Neck Neoplasms - genetics Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - pathology Hematology Humans Internal Medicine Male Medicine Medicine & Public Health Middle Aged Mucosa Mutation Mutation hot spots Oncology Oral cavity Original Article – Cancer Research Original – Cancer Research Polymerase chain reaction Promoter Regions, Genetic Prospective Studies RNA-directed DNA polymerase Squamous cell carcinoma Squamous Cell Carcinoma of Head and Neck - genetics Squamous Cell Carcinoma of Head and Neck - metabolism Squamous Cell Carcinoma of Head and Neck - pathology Survival Analysis Telomerase Telomerase - genetics Telomerase - metabolism Telomerase reverse transcriptase Telomere - genetics Telomere - metabolism Telomere - pathology Telomeres Tumors Yeast |
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| Title | TERT promoter hotspot mutations and their relationship with TERT levels and telomere erosion in patients with head and neck squamous cell carcinoma |
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