Mutations in TERT promoter and FGFR3 and telomere length in bladder cancer. Issue 7 (7th April 2015)

• Record Type: Journal Article
• Authors: Hosen, Ismail; Rachakonda, P. Sivaramakrishna; Heidenreich, Barbara; de Verdier, Petra J.; Ryk, Charlotta; Steineck, Gunnar; Hemminki, Kari; Kumar, Rajiv
• Is Part Of: International journal of cancer. Volume 137:Issue 7(2015:Oct. 01)
• Page Start: 1621
• Page End: 1629
• Publication Date: 2015-04-07
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29526
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Mutations in the promoter of the <italic>telomerase reverse transcriptase</italic> (<italic>TERT</italic>) and <italic>fibroblast growth factor receptor 3</italic> (<italic>FGFR3)</italic> genes constitute the most recurrent somatic alterations in urothelial carcinoma of bladder. In this study, we screened DNA from 327 urothelial bladder carcinomas from well‐documented patients, with different stages and grades and known <italic>TERT</italic> promoter mutational status, for <italic>FGFR3</italic> alterations and measured relative telomere length (RTL). Although, the frequency of the <italic>TERT</italic> promoter mutations was higher than those in <italic>FGFR3</italic>; however, the alterations at the two loci occurred together more frequently than per chance [Odds ratio (OR) = 4.93, 95% CI = 2.72–8.92, <italic>p</italic> < 0.0001]. While tumors with <italic>TERT</italic> promoter and <italic>FGFR3</italic> mutations had shorter RTL than those without mutations (<italic>p</italic> < 0.0001), the <italic>TERT</italic> promoter mutations in conjunction with the common allele of the rs2853669 polymorphism defined sub‐group of patients with an observed decreased overall survival (OR = 2.15, 95% CI = 1.00–4.61) and increased recurrence in patients with TaG1+TaG2 disease categories (OR = 3.68, 95%CI = 1.12–12.05). The finding of shorter telomeres in tumors with <italic>TERT</italic> promoter and/or <italic>FGFR3</italic> mutations than without mutations implies mechanistic relevance of telomere biology in cancer progression. The observed association with recurrence and survival shows that the <italic>TERT</italic> promoter mutations can potentially be used as markers to refine selection of patients for different treatments. The overwhelming frequency of the <italic>TERT</italic> promoter mutations also represents a case for development of an eventual therapeutic target.</p> </abstract>