Prevalence and potentially prognostic value of C-circles associated with alternative lengthening of telomeres in canine appendicular osteosarcoma.
C-circle assay
comparative oncology
human and dog
osteosarcoma
prognosis
telomere maintenance mechanism
Journal
Veterinary and comparative oncology
ISSN: 1476-5829
Titre abrégé: Vet Comp Oncol
Pays: England
ID NLM: 101185242
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
revised:
16
11
2020
received:
11
09
2020
accepted:
17
11
2020
pubmed:
20
11
2020
medline:
22
1
2022
entrez:
19
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33211388
doi: 10.1111/vco.12665
pmc: PMC8247038
doi:
Substances chimiques
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
222-231Informations de copyright
© 2020 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.
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