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Molecular characterisation of canine osteosarcoma in high risk breeds

Simpson, Siobhan; Dunning, Mark; de Brot, Simone; Alibhai, Aziza; Bailey, Clara; Woodcock, Corinne L.; Mestas, Madeline; Akhtar, Shareen; Jeyapalan, Jennie N.; Lothion-Roy, Jennifer; Emes, Richard D.; Allegrucci, Cinzia; Rizvanov, Albert A.; Mongan, Nigel P.; Rutland, Catrin S.

Molecular characterisation of canine osteosarcoma in high risk breeds Thumbnail


Siobhan Simpson

Simone de Brot

Aziza Alibhai

Clara Bailey

Corinne L. Woodcock

Madeline Mestas

Shareen Akhtar

Jennifer Lothion-Roy

Richard D. Emes

Albert A. Rizvanov

Professor of Oncology


© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Dogs develop osteosarcoma (OSA) and the disease process closely resembles that of human OSA. OSA has a poor prognosis in both species and disease-free intervals and cure rates have not improved in recent years. Gene expression in canine OSAs was compared with non-tumor tissue utilising RNA sequencing, validated by qRT-PCR and immunohistochemistry (n = 16). Polymorphic polyglutamine (polyQ) tracts in the androgen receptor (AR/NR3C4) and nuclear receptor coactivator 3 (NCOA3) genes were investigated in control and OSA patients using polymerase chain reaction (PCR), Sanger sequencing and fragment analysis (n = 1019 Rottweilers, 379 Irish Wolfhounds). Our analysis identified 1281 significantly differentially expressed genes (>2 fold change, p < 0.05), specifically 839 lower and 442 elevated gene expression in osteosarcoma (n = 3) samples relative to non-malignant (n = 4) bone. Enriched pathways and gene ontologies were identified, which provide insight into the molecular pathways implicated in canine OSA. Expression of a subset of these genes (SLC2A1, DKK3, MMP3, POSTN, RBP4, ASPN) was validated by qRTPCR and immunohistochemistry (MMP3, DKK3, SLC2A1) respectively. While little variation was found in the NCOA3 polyQ tract, greater variation was present in both polyQ tracts in the AR, but no significant associations in length were made with OSA. The data provides novel insights into the molecular mechanisms of OSA in high risk breeds. This knowledge may inform development of new prevention strategies and treatments for OSA in dogs and supports utilising spontaneous OSA in dogs to improve understanding of the disease in people.

Journal Article Type Article
Acceptance Date Aug 14, 2020
Online Publication Date Aug 25, 2020
Publication Date Sep 1, 2020
Deposit Date Aug 21, 2020
Publicly Available Date Aug 25, 2020
Journal Cancers
Electronic ISSN 2072-6694
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 12
Issue 9
Article Number 2405
Keywords Androgen; Androgen receptor; Bone; Cancer risk; Canine; KEGG; Wiki
Public URL
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