title: Alternative lengthening of telomeres does exist in various canine sarcomas.
abstract: Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism (TMM) found in some human tumors such as sarcomas. Canine tumors are not characterized for ALT and the study aim was to identify if the ALT phenotype exists in canine sarcomas. Sixty-four canine sarcoma samples (20 snap-frozen, 44 FFPE) as well as six canine sarcoma cell lines were screened for ALT by C-circle assay. ALT was further evaluated by measuring telomere length via qPCR and telomere restriction-fragments including pulsed-field electrophoresis. ALT-associated proteins were validated by immunohistochemistry. Further, telomerase activity (TA) and gene expression were analyzed by TRAP and qPCR. DNA from 20 human neuroblastomas and 8 sarcoma cell lines served as comparative controls. ALT was detected in 9.4% (6/64) canine sarcomas including aggressive subtypes as hemangiosarcoma, osteosarcoma, and histiocytic sarcoma. C-circle levels were comparable with human ALT-positive controls. All ALT tumors demonstrated loss of ATRX expression and 5/6 showed strong p53 expression. TA was detected in 93% (14/15) snap-frozen samples including a sarcoma with ALT activity. This tumor showed long heterogeneous telomeres, and a high level of colocalization of DAXX with telomeres. One sarcoma was ALT and TA negative. All canine and human sarcoma cell lines were ALT negative. In this study, we demonstrated that canine sarcomas use ALT. As in humans, ALT was identified in aggressive sarcomas subtypes and coexisted with TA in one tumor. Overall, canine sarcomas seem to share many similarities with their human counterparts and appear an attractive model for comparative telomere research. © 2016 Wiley Periodicals, Inc.
authors: Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria.|Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors: Theresa
authors: T
authors: Kreilmeier
authors: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors: Sandra
authors: S
authors: Sampl
authors: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors: Abigail J
authors: AJ
authors: Deloria
authors: Vet Core Facility, University of Veterinary Medicine Vienna, Vienna, Austria.
authors: Ingrid
authors: I
authors: Walter
authors: Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, Austria.
authors: Martin
authors: M
authors: Reifinger
authors: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
authors: Marlene
authors: M
authors: Hauck
authors: Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.
authors: Luke B
authors: LB
authors: Borst
authors: Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors: Klaus
authors: K
authors: Holzmann
authors: Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria.
authors: Miriam
authors: M
authors: Kleiter
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics* / Q000473:pathology; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D012509:Sarcoma / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000075924:X-linked Nuclear Protein
chemical_list: D009687:Nuclear Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: cancer; comparative; dog; non-determined TMM; telomerase-independent; telomere length