Department for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Austria.
Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
Vet Comp Oncol. 2021 Jun;19(2):222-231. doi: 10.1111/vco.12665. Epub 2020 Dec 8.
Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism (TMM) with high prevalence in human osteosarcomas but remains unknown in canine osteosarcomas. The aim of this study was to evaluate the prevalence of ALT by detection of extra-chromosomal circles of telomeric DNA and to assess clinical outcome in canine patients with spontaneous occurring appendicular osteosarcoma. Fifty dogs with histopathological confirmed osteosarcomas were included into this study. Medical records were retrospectively analysed for patient characteristics, oncologic therapy and survival. DNA was isolated from archived FFPE tumour tissue specimens and applied for C- and G-circle assay (CCA and GCA) and for telomeric content (TC) measurement with radiolabeled probes. ALT activity was detected for 10 of 50 (20%) cases by CCA. Four CCA positive cases were detected even with input DNA below 1 ng and demonstrated the high sensitivity of CCA for canine tumours. G-circles and TC were not suitable to distinguish CCA positive and negative cases. CCA-status showed an association with male gender and Rottweiler breed. Dogs with CCA positive osteosarcomas had shorter overall survival times than patients with CCA-tumours and CCA-status was a significant prognostic factor besides treatment in the Cox proportional hazard model. These findings make canine osteosarcomas an interesting model for comparative TMM research, but future studies are warranted to investigate if CCA-status can serve as novel prognostic marker.
端粒的非经典延长（ALT）是一种端粒酶独立的端粒维持机制（TMM），在人类骨肉瘤中很常见，但在犬骨肉瘤中尚不清楚。本研究旨在通过检测端粒 DNA 的额外染色体环来评估 ALT 的流行率，并评估犬自发性附肢骨肉瘤患者的临床结果。本研究纳入了 50 例经组织病理学证实的骨肉瘤犬。回顾性分析了患者特征、肿瘤治疗和生存情况的病历记录。从存档的 FFPE 肿瘤组织标本中提取 DNA，用于 C 和 G 环检测（CCA 和 GCA）和端粒含量（TC）测量，使用放射性标记探针。通过 CCA 检测到 50 例中的 10 例（20%）存在 ALT 活性。即使输入 DNA 低于 1ng，也检测到了 4 个 CCA 阳性病例，这表明 CCA 对犬肿瘤具有很高的灵敏度。G 环和 TC 不适合区分 CCA 阳性和阴性病例。CCA 状态与雄性性别和罗威纳犬种有关。CCA 阳性骨肉瘤犬的总生存时间短于 CCA 肿瘤犬，并且 CCA 状态是 Cox 比例风险模型中除治疗外的一个重要预后因素。这些发现使犬骨肉瘤成为一种有趣的比较 TMM 研究模型，但需要进一步的研究来探讨 CCA 状态是否可以作为一种新的预后标志物。
