title: TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.
abstract: 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.
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600113, India.
authors.forename: Vilvanathan
authors.initials: V
authors.lastname: Vinothkumar
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600113, India.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Arunkumar
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600113, India.
authors.forename: Sundaramoorthy
authors.initials: S
authors.lastname: Revathidevi
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600113, India.
authors.forename: Kanagaraj
authors.initials: K
authors.lastname: Arun
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600113, India.
authors.forename: Mayakannan
authors.initials: M
authors.lastname: Manikandan
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600113, India.
authors.forename: Arunagiri Kuha Deva Magendhra
authors.initials: AK
authors.lastname: Rao
authors.affiliation: Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College, Chennai, 600014, India.
authors.forename: Kottayasamy Seenivasagam
authors.initials: KS
authors.lastname: Rajkumar
authors.affiliation: Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College, Chennai, 600014, India.
authors.forename: Chandrasekar
authors.initials: C
authors.lastname: Ajay
authors.affiliation: Centre for Oncology, Government Royapettah Hospital & Kilpauk Medical College, Chennai, 600014, India.
authors.forename: Ramamurthy
authors.initials: R
authors.lastname: Rajaraman
authors.affiliation: Institute of Social Obstetrics and Government Kasturba Gandhi Hospital for Women and Children, Chennai, 600005, India.
authors.forename: Rajendren
authors.initials: R
authors.lastname: Ramani
authors.affiliation: Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia.
authors.forename: Avaniyapuram Kannan
authors.initials: AK
authors.lastname: Murugan
authors.affiliation: Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, 600113, India. akmunirajan@gmail.com.
authors.forename: Arasambattu Kannan
authors.initials: AK
authors.lastname: Munirajan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000077195:Squamous Cell Carcinoma of Head and Neck; D019098:Telomerase / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D019098:Telomerase
keywords: Cervical cancer; Human papilloma virus; Oral cancer; Promoter mutation; Telomerase reverse transcriptase