title: TERT promoter mutations in clear cell renal cell carcinoma.
abstract: We screened promoter region of the telomerase reverse transcriptase (TERT) for activating somatic mutations in 188 tumors from patients with clear cell renal cell carcinoma (ccRCC). Twelve tumors (6.4%) carried a mutation within the core promoter region of the gene. The mutations were less frequent in high grade tumors compared to low grade tumors [odds ratio (OR) = 0.15, 95% confidence interval (CI) = 0.03-0.72, p = 0.02]. Multivariate analysis for cause specific survival showed statistically significant poor outcome in patients with TERT promoter mutations [hazard ratio (HR) = 2.90, 95% CI = 1.13-7.39, p = 0.03]. A common polymorphism (rs2853669) within the locus seemed to act as a modifier of the effect of the mutations on patient survival as the noncarriers of the variant allele with the TERT promoter mutations showed worst survival (HR = 3.34, 95% CI = 1.24-8.98, p = 0.02). We also measured relative telomere length (RTL) in tumors and difference between tumors with and without the TERT promoter mutations was not statistically significant. Similarly, no difference in patient survival based on RTL in tumors was observed. Our study showed a relatively low frequency of TERT promoter mutations in ccRCC. Nevertheless, patients with the mutations, particularly in the absence of the rs2853669 variant showed the worst disease-specific survival. Thus, it is possible that the TERT promoter mutations define a small subset of tumors with an aggressive behavior.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ismail
authors.initials: I
authors.lastname: Hosen
authors.forename: P Sivaramakrishna
authors.initials: PS
authors.lastname: Rachakonda
authors.forename: Barbara
authors.initials: B
authors.lastname: Heidenreich
authors.forename: Raviprakash T
authors.initials: RT
authors.lastname: Sitaram
authors.forename: Börje
authors.initials: B
authors.lastname: Ljungberg
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000378:metabolism*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: TERT promoter mutations; mutations; survival; telomere length