Abstract
Abstract We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients within the core promoter region of the telomerase reverse transcriptase (TERT) gene1. Both the germline mutation at -57 bp from ATG start site and somatic mutations at -124 bp, -124/-125 bp, -138/-139 bp and -146 bp from ATG result in de novo creation of Ets/TCF transcription factor binding motifs that lead to the increased gene expression. Subsequent studies have shown that TERT promoter mutations are not only confined to melanoma and are rather recurrent in different cancer types that include bladder cancer, glioma, hepatocellular carcinoma and others. In this study we show the difference in pattern of the TERT promoter mutations between melanoma and bladder cancer. While in melanoma the -146 C>T mutation is the most frequent detected somatic base change in the TERT promoter, the -124 C>T mutation is overwhelmingly the most common mutation in bladder cancer. In melanoma CC>TT tandem mutations at -124/-125 bp and -138/-139 bp positions from ATG constitute about 10 percent of the detected TERT promoter mutations whereas in bladder cancer we did not detect any tandem mutations. The differences in the mutational pattern reflect etiological differences between the cancer types. In conclusion, the pattern of mutations in the TERT promoter differ between the cancer types even though all common mutations within the TERT promoter result in de novo creation of a common CCGGAA/T motif for Ets/TCF transcription factors. 1Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R. TERT promoter mutations in familial and sporadic melanoma. Science. 2013;22:339:959-961. Citation Format: Rajiv Kumar, Barbara Heidenreich, Ismail Hosen, Sivaramakrishna Rachakonda, Kari Hemminki. Patterns of Telomerase reverse transcriptase (TERT) promoter mutations in melanoma and bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 559. doi:10.1158/1538-7445.AM2014-559
Published Version
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