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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Vydané v:Journal of cancer research and clinical oncology Ročník 146; číslo 2; s. 381 - 389
Hlavní autori: Boscolo-Rizzo, Paolo, Giunco, Silvia, Rampazzo, Enrica, Brutti, Martina, Spinato, Giacomo, Menegaldo, Anna, Stellin, Marco, Mantovani, Monica, Bandolin, Luigia, Rossi, Marco, Del Mistro, Annarosa, Tirelli, Giancarlo, Dei Tos, Angelo Paolo, Guerriero, Angela, Niero, Monia, Da Mosto, Maria Cristina, Polesel, Jerry, De Rossi, Anita
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2020
Springer Nature B.V
Predmet:
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
Promoter
Head and neck squamous cell carcinoma
Telomerase reverse transcriptase
Mutation
Telomere
ISSN:0171-5216, 1432-1335, 1432-1335
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0171-5216
1432-1335
1432-1335
DOI:10.1007/s00432-020-03130-z