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Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma
Author(s) -
Annunziata Clorinda,
Pezzuto Francesca,
Greggi Stefano,
Ionna Franco,
Losito Simona,
Botti Gerardo,
Buonaguro Luigi,
Buonaguro Franco M.,
Tornesello Maria Lina
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31412
Subject(s) - telomerase , telomerase reverse transcriptase , promoter , cervical intraepithelial neoplasia , microbiology and biotechnology , gene , hela , cancer research , biology , cervical cancer , mutation , adenocarcinoma , carcinoma , gene expression , cancer , cell culture , genetics
Two recurrent mutations (–124 G > A and −146 G > A) in the core promoter region of the human telomerase reverse transcriptase ( TERT ) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C‐4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.3% of oral squamous cell carcinoma (SCC) and 16.8% of cervical SCC harboured mutually exclusive G to A transitions at nucleotide position −124 or −146. TERT promoter was mutated at nucleotide −146 (G > A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of TERT gene was significantly higher in TERT promoter mutated (–124G > A or −146G > A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that TERT promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on TERT expression.