The ribonucleoprotein complex telomerase provides the physiological mechanism that maintains telomere length by adding repetitive hexanucleotide repeats with the sequence 5′-TTAGGG-3′ to telomeres. Reactivation of telomerase has been observed in the majority of human cancers . In this context, telomerase reverse transcriptase (TERT) serves as the catalytic subunit of the telomerase complex and has been shown to contribute to the immortalization
of cancer cells . However, the underlying mechanism of TERT reactivation in cancer cells was an unresolved issue . Recently, highly recurrent somatic mutations in the promoter region of the TERT gene have been detected . The most frequent mutations PRI-724 manufacturer were a single cytosine exchange to IKK inhibitor thymine at chromosome 5 base position 1,295,228 (C228T) or less frequently at base position 1,295,250 (C250T) (-124 and -146 bp from ATG start site,
respectively). These TERT mutations lead to a new binding motif for E-twenty six/ternary complex factors (Ets/TCF) transcription factors and results in an up to SB-715992 datasheet 4-fold increase of TERT promoter activity in reporter gene assays [11, 12]. First described in melanomas [11, 12], TERT promoter mutations have subsequently been found in many other human cancer types, with highest frequencies in subtypes of CNS tumors, in a number of malignancies of epithelial origin including bladder carcinomas, thyroid carcinomas, and hepatocellular carcinomas, and in atypical fibroxanthomas and in dermal pleomorphic sarcomas [13–26]. Accordingly, TERT promoter mutations belong to the most common somatic learn more genetic lesions in human cancers. A study by Killela et al. investigated a broad range of human cancers for TERT promoter mutations, including soft tissue sarcomas . However, the case number of single STS entities was limited
and a number of subtypes were not comprised. Therefore, the present study was conducted to investigate the prevalence of TERT promoter mutations in a comprehensive series of 341 soft tissue tumors comprised of 16 types including rare entities and in 16 cell lines of seven sarcoma types. Further, we looked for associations, if any, with clinicopathological parameters. Materials and methods Sarcoma samples and clinicopathological characteristics The sarcoma tissue samples were collected at the Institute of Pathology, University of Heidelberg, and diagnoses were confirmed by three sarcoma pathologists (GM, WH and EW). Diagnoses were based on standard histopathological criteria in conjunction with immunohistological and molecular analysis according to the current WHO classification of tumors . Only samples with at least 80% vital tumor cells were selected for the analysis. The study was approved by the ethics committee, medical faculty of heidelberg University (No. 206/2005, 207/2005). The clinicopathological characteristics are shown in Additional file 1: Table S1.