TERT promoter mutations in clear cell renal cell carcinoma. Issue 10 (30th October 2014)

• Record Type: Journal Article
• Authors: Hosen, Ismail; Rachakonda, P. Sivaramakrishna; Heidenreich, Barbara; Sitaram, Raviprakash T.; Ljungberg, Börje; Roos, Göran; Hemminki, Kari; Kumar, Rajiv
• Is Part Of: International journal of cancer. Volume 136:Issue 10(2015:May 15)
• Page Start: 2448
• Page End: 2452
• Publication Date: 2014-10-30
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29279
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>We screened promoter region of the <italic>telomerase reverse transcriptase</italic> (<italic>TERT</italic>) 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, <italic>p</italic> = 0.02]. Multivariate analysis for cause specific survival showed statistically significant poor outcome in patients with <italic>TERT</italic> promoter mutations [hazard ratio (HR) = 2.90, 95% CI = 1.13–7.39, <italic>p</italic> = 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 <italic>TERT</italic> promoter mutations showed worst survival (HR = 3.34, 95% CI = 1.24–8.98, <italic>p</italic> = 0.02). We also measured relative telomere length (RTL) in tumors and difference between tumors with and without the <italic>TERT</italic> 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 <italic>TERT</italic> 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 <italic>TERT</italic> promoter mutations define a small subset of tumors with an aggressive behavior.</p> </abstract>