{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:29:22Z","timestamp":1760149762444,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cancer cells activate telomere maintenance mechanisms (TMMs) to overcome senescence and thus are targets for TMM-specific therapies. Telomerase-independent alternative lengthening of telomeres (ALT) is frequently utilized as a TMM in human sarcoma subtypes. Histiocytic sarcoma (HS) is a rare but aggressive tumor of hematopoietic origin with unknown ALT incidence in humans. ALT has been identified in canine HS, a tumor type comparable to human HS that occurs with high rates in certain canine breeds such as Bernese mountain dogs (BMDs). This retrospective study characterized the frequency of ALT in BMD and non-BMD patients diagnosed with HS as surrogates for humans. Formalin-fixed paraffin-embedded tumor samples from 63 dogs at two centers, including 47 BMDs, were evaluated for their ALT activity and relative telomere content (TC) using a radiolabel C-circle assay (CCA). Known ALT-positive samples served as controls. CCA-positive cases were validated via FISH. Two BMD samples showed ALT activity of 1\u201314% compared to controls. All other samples were ALT-negative. The TC did not correlate with the CCA results. ALT positivity was validated by the appearance of ultrabright telomere foci. Low ALT activity was present in 4% of BMDs with HS and therefore does not appear to be a common target for therapeutic approaches but can have diagnostic value.<\/jats:p>","DOI":"10.3390\/cancers15174214","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T08:01:21Z","timestamp":1692777681000},"page":"4214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alternative Lengthening of Telomeres Is Rare in Canine Histiocytic Sarcoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5346-2821","authenticated-orcid":false,"given":"Theresa","family":"Kreilmeier-Berger","sequence":"first","affiliation":[{"name":"Department for Companion Animals and Horses, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike","family":"Aupperle-Lellbach","sequence":"additional","affiliation":[{"name":"Laboklin GmbH & Co. KG, 97688 Bad Kissingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Reifinger","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8245-7740","authenticated-orcid":false,"given":"Nicolai Valentin","family":"H\u00f6rstke","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-3377","authenticated-orcid":false,"given":"Klaus","family":"Holzmann","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Kleiter","sequence":"additional","affiliation":[{"name":"Department for Companion Animals and Horses, University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/345458a0","article-title":"Telomeres Shorten during Ageing of Human Fibroblasts","volume":"345","author":"Harley","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The Hallmarks of Cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.tvjl.2007.01.024","article-title":"Telomeres and Telomerase: Biological and Clinical Importance in Dogs","volume":"175","author":"Nasir","year":"2008","journal-title":"Vet. 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