Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

Intravenous thrombolysis before endovascular therapy for large vessel strokes can lead to significantly higher hospital costs without improving outcomes

Background Limited efficacy of IV recombinant tissue plasminogen activator (rt-PA) for large vessel occlusions (LVO) raises doubts about its utility prior to endovascular therapy. Purpose To compare outcomes and hospital costs for anterior circulation LVOs (middle cerebral artery, internal carotid artery terminus (ICA-T)) treated with either primary endovascular therapy alone (EV-Only) or bridging therapy (IV+EV)). Methods A single-center retrospective analysis was performed. Clinical and demographic data were collected prospectively and relevant cost data were obtained for each patient in the study. Results 90 consecutive patients were divided into EV-Only (n=52) and IV+EV (n=38) groups. There was no difference in demographics, stroke severity, or clot distribution. The mean (SD) time to presentation was 5:19 (4:30) hours in the EV-Only group and 1:46 (0:52) hours in the IV+EV group (