title: Clinical Characteristics and Prognostic Significance of TERT Promoter Mutations in Cancer: A Cohort Study and a Meta-Analysis.
abstract: BACKGROUND
  The prevalence of telomerase reverse transcriptase (TERT) promoter mutations (pTERTm) in non-small-cell lung cancer (NSCLC) have been investigated, but the results were inconsistent. In addition, several studies have analysed the role of pTERTm in the etiology of various types of cancers, however, the results also remain inconsistent.
  
  
  METHODS
  The genomic DNA sequence of 103 NSCLC samples were analysed to investigate the frequency of pTERTm in these patients and to establish whether these mutations are associated with their clinical data. Furthermore, a meta-analysis based on previously published articles and our cohort study was performed to investigate the association of pTERTm with patient gender, age at diagnosis, metastasis status, tumour stage and cancer prognosis (5-year overall survival rate).
  
  
  RESULTS
  In the cohort study, 4 patients had C228T and 2 had C250T, with a total mutation frequency up to 5.8%. Significant difference of clinical data between pTERTm carriers and noncarriers was only found in age at diagnosis. In the meta-analysis, We found that pTERTm carriers in cancer patients are older than noncarriers (Mean difference (MD) = 5.24; 95% confidence interval [CI], 2.00 to 8.48), male patients were more likely to harbour pTERTm (odds Ratios (OR) = 1.38; 95% CI, 1.22 to 1.58), and that pTERTm had a significant association with distant metastasis (OR = 3.78; 95% CI, 2.45 to 5.82), a higher tumour grade in patients with glioma (WHO grade III, IV vs. I, II: OR, 2.41; 95% CI, 1.88 to 3.08) and a higher tumour stage in other types of cancer (III, IV vs. I, II: OR, 2.48; 95% CI, 1.48 to 4.15). pTERTm was also significantly associated with a greater risk of death (hazard ratio = 1.71; 95% CI, 1.41 to 2.08).
  
  
  CONCLUSIONS
  pTERTm are a moderately prevalent genetic event in NSCLC. The current meta-analysis indicates that pTERTm is associated with patient age, gender and distant metastasis. It may serves as an adverse prognostic factor in individuals with cancers.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 310003.
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 310003.
authors.forename: Jin-lin
authors.initials: JL
authors.lastname: Cao
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 310003.
authors.forename: Abudumailamu
authors.initials: A
authors.lastname: Abuduwufuer
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 310003.
authors.forename: Lu-Ming
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 310003.
authors.forename: Xiao-Shuai
authors.initials: XS
authors.lastname: Yuan
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 310003.
authors.forename: Wang
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, 310003.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D002648:Child; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005910:Glioma / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008545:Melanoma / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D019098:Telomerase / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: C509186:TERT protein, human; D019098:Telomerase