title: The promise of telomere length, telomerase activity and its regulation in the translocation-dependent cancer ESFT; clinical challenges and utility.
abstract: The Ewing's sarcoma family of tumours (ESFT) are diagnosed by EWS-ETS gene translocations. The resulting fusion proteins play a role in both the initiation and maintenance of these solid aggressive malignant tumours, suppressing cellular senescence and increasing cell proliferation and survival. EWS-ETS fusion proteins have altered transcriptional activity, inducing expression of a number of different target genes including telomerase. Up-regulation of hTERT is most likely responsible for the high levels of telomerase activity in primary ESFT, although telomerase activity and expression of hTERT are not predictive of outcome. However levels of telomerase activity in peripheral blood may be useful to monitor response to some therapeutics. Despite high levels of telomerase activity, telomeres in ESFT are frequently shorter than those of matched normal cells. Uncertainty about the role that telomerase and regulators of its activity play in the maintenance of telomere length in normal and cancer cells, and lack of studies examining the relationship between telomerase activity, regulators of its activity and their clinical significance in patient samples have limited their introduction into clinical practice. Studies in clinical samples using standardised assays are critical to establish how telomerase and regulators of its activity might best be exploited for patient benefit.
authors.affiliation: Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Proctor
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Brownhill
authors.forename: Susan A
authors.initials: SA
authors.lastname: Burchill
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D016922:Cellular Senescence; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D019098:Telomerase / Q000096:biosynthesis*; D016615:Telomere / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase