title: Functional evaluation of TERT-CLPTM1L genetic variants associated with susceptibility of papillary thyroid carcinoma.
abstract: TERT is the catalytic subunit of telomerase which plays an essential part in cellular immortality by maintaining telomere integrity. TERT is commonly over-expressed in human malignancies, indicating its key role in cell transformation. The chromosome 5p15.33 TERT-CLPTM1L region has been associated with susceptibility of multiple cancers via a genome-wide association approach. However, the involvement of this locus in papillary thyroid carcinoma (PTC) etiology is still largely unknown. We analyzed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) of the TERT-CLPTM1L region in a two stage case-control design. After genotyping 2300 PTC patients and frequency-matched 2300 unaffected controls, we found that TERT rs2736100 genetic variant is significantly associated with elevated PTC risk. Ex vivo reporter gene assays indicated that the PTC susceptibility rs2736100 polymorphism locating in a potential TERT intronic enhancer has a genotype-specific effect on TERT expression. Correlations between rs2736100 genotypes and tissue-specific TERT expression supported the regulatory function of this genetic variant in vivo. Our data demonstrated that the functional TERT rs2736100 SNP as a novel genetic component of PTC etiology. This study, together with recent studies in other cancers, unequivocally establishes an essential role of TERT in cancers.
authors.affiliation: Department of Head and Neck Surgery, Zhejiang Province Cancer Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Ge
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Head and Neck Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Changming
authors.initials: C
authors.lastname: An
authors.affiliation: Key Laboratory of Fertility Preservation and Maintenance (Ministry of Education), Ningxia Medical University, Yinchuan, Ningxia, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Head and Neck Surgery, Zhejiang Province Cancer Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lv
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hematology, National Center for Clinical Laboratories and Beijing Hospital, Beijing, China.
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Du
authors.affiliation: Shandong Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D000328:Adult; D002291:Carcinoma, Papillary / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: C422445:CLPTM1L protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase