TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas
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Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient’s clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers.
KeywordsTelomerase reverse transcriptase Cervical cancer Oral cancer Promoter mutation Human papilloma virus
We thank Dr. Sindhuja, Mrs. Arivazhagi (Arignar Anna Memorial Cancer Hospital & Research Institute, Kanchipuram), and Dr. V. Rajalakshmi (Institute of Obstetrics & Gynaecology and Government General Hospital for Women and Children, Chennai) for clinical assessment and sample collection. We, VV, KA, MM, AKD, and GA gratefully acknowledge the Government of India’s Council of Scientific and Industrial Research (CSIR) and University Grant Commission (UGC), respectively, for providing research fellowships. We also thank DST-FIST and UGC-SAP infrastructure facilities.
Compliance with ethical standards
Conflicts of interest
The Institutional Ethics Committee, Government Arignar Anna Memorial Cancer Hospital, Kancheepuram (No.101041/e1/2009-2), and the Madras Medical College, Chennai (No.04092010), approved the present study. Cervical and oral cancer samples were collected following the Institutional Ethical Committee (IEC) guidelines and informed consent was obtained from each patient, after explaining about the research study. For the illiterate patients, the study was verbally explained and consent was obtained with their thumb impression.
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