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Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes.
Συγγραφείς: Moberg IM; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway., Hansen N; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway., Bergholtz H; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Borge KS; LINK Medical Research AS, Oslo, Norway., Gunnes G; Pathology Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway., Arnet EF; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway., Guttersrud OA; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway., Solbakken MH; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway., Lingaas F; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.
Πηγή: Veterinary and comparative oncology [Vet Comp Oncol] 2026 Sep; Vol. 24 (3), pp. 444-457. Date of Electronic Publication: 2026 Apr 16.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Blackwell Country of Publication: England NLM ID: 101185242 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5829 (Electronic) Linking ISSN: 14765810 NLM ISO Abbreviation: Vet Comp Oncol Subsets: MEDLINE
Imprint Name(s): Original Publication: Oxford, UK : Blackwell, [2003]-
Ιατρικοί όροι (MeSH): Mammary Neoplasms, Animal*/pathology , Mammary Neoplasms, Animal*/genetics , Mammary Neoplasms, Animal*/classification , Mammary Neoplasms, Animal*/metabolism , Dog Diseases*/pathology , Dog Diseases*/genetics , Dog Diseases*/metabolism , Dog Diseases*/classification , Gene Expression Profiling*/veterinary , Transcriptome*, Animals ; Dogs ; Female ; Gene Expression Regulation, Neoplastic
Περίληψη: This study presents a comprehensive transcriptomic analysis of 128 canine mammary tumours (CMTs), aiming to characterize their molecular landscape. Differential gene expression analysis (DGE), gene set enrichment analysis (GSEA) and clustering based on the human PAM50 gene panel were applied to explore molecular differences between the different histological categories. The analysis revealed transcriptomic differences between benign and malignant tumours as well as between tumours with high and low mitotic count. Malignant tumours were significantly enriched for gene sets associated with cell cycle regulation, proliferation, inflammatory response, signalling pathways and metabolic processes. Of the malignant tumours, purely epithelial tumours were enriched in gene sets related to proliferation, signalling and metabolic processes when compared to mixed tumours harbouring myoepithelial or mesenchymal components. To assess the relevance of human classification systems, CMTs were clustered on the PAM50 genes. The analysis revealed two clusters resembling human basal-like and luminal A subtypes, while the remaining tumours did not display expression patterns similar to human breast cancer subtypes. This suggests that there are limitations to applying the human molecular classification systems to canine tumours without adaptation. Additionally, CMTs displayed intragroup heterogeneity, where not all tumours within a histopathological category clustered together, indicating that the molecular aspect of CMTs is not necessarily reflected in the pathology. Together, this study highlights the need to develop canine-specific molecular markers based on gene expression, which could enable diagnosis prior to surgical removal of tumours, and ultimately improve treatment strategies and outcomes for dogs with mammary tumours.
(© 2026 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)
References: Vet Comp Oncol. 2009 Sep;7(3):162-72. (PMID: 19691645)
J Reprod Fertil Suppl. 2001;57:439-43. (PMID: 11787188)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Animals (Basel). 2021 Jul 12;11(7):. (PMID: 34359206)
Vet Pathol. 2020 Nov;57(6):774-790. (PMID: 32807036)
J Clin Oncol. 2009 Mar 10;27(8):1160-7. (PMID: 19204204)
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517)
J Mammary Gland Biol Neoplasia. 2022 Jun;27(2):171-183. (PMID: 35932380)
Biomed Pharmacother. 2023 Jul;163:114822. (PMID: 37146418)
ISRN Oncol. 2012;2012:450267. (PMID: 23227362)
J Coll Physicians Surg Pak. 2018 Oct;28(10):783-790. (PMID: 30266125)
Nucleic Acids Res. 2025 Jan 11;53(2):. (PMID: 39844453)
Bioinformatics. 2014 Mar 15;30(6):801-7. (PMID: 22321699)
Biofilm. 2021 Jan 13;3:100043. (PMID: 33665610)
PLoS One. 2015 May 08;10(5):e0126371. (PMID: 25955013)
Vet Rec. 2010 May 8;166(19):586-90. (PMID: 20453236)
JCO Precis Oncol. 2017 Jul;2017:. (PMID: 28890946)
Nature. 2000 Aug 17;406(6797):747-52. (PMID: 10963602)
Vet Pathol. 2024 Sep;61(5):752-764. (PMID: 38533804)
Imeta. 2022 Aug 01;1(3):e43. (PMID: 38868715)
Front Oncol. 2020 Apr 28;10:617. (PMID: 32411603)
Vet Pathol. 2013 Jan;50(1):94-105. (PMID: 22688585)
Cell Syst. 2015 Dec 23;1(6):417-425. (PMID: 26771021)
Vet Sci. 2025 Feb 19;12(2):. (PMID: 40005948)
Nat Rev Genet. 2009 Jan;10(1):57-63. (PMID: 19015660)
Vet Med Int. 2024 May 10;2024:9319651. (PMID: 38766503)
Signal Transduct Target Ther. 2024 Aug 21;9(1):205. (PMID: 39164274)
Cancer Res. 2014 Sep 15;74(18):5045-56. (PMID: 25082814)
Vet Sci. 2023 May 30;10(6):. (PMID: 37368765)
Vet Pathol. 2011 Jan;48(1):117-31. (PMID: 21266722)
BMC Genomics. 2009 Mar 27;10:135. (PMID: 19327144)
Vet J. 2024 Feb;303:106055. (PMID: 38097103)
Cancer Discov. 2022 Jan;12(1):31-46. (PMID: 35022204)
Animals (Basel). 2023 Oct 09;13(19):. (PMID: 37835752)
Breast Cancer Res. 2023 Oct 3;25(1):114. (PMID: 37789381)
Vet Comp Oncol. 2026 Sep;24(3):444-457. (PMID: 41992075)
Brief Bioinform. 2021 Nov 5;22(6):. (PMID: 34329375)
PLoS One. 2021 Nov 22;16(11):e0260400. (PMID: 34807950)
Nat Commun. 2020 Mar 6;11(1):1234. (PMID: 32144251)
Nat Commun. 2020 Jul 17;11(1):3616. (PMID: 32680987)
Histopathology. 2023 Jan;82(1):5-16. (PMID: 36482272)
BMC Bioinformatics. 2016 Nov 25;17(1):483. (PMID: 27884101)
Vet Pathol. 2016 Jan;53(1):7-9. (PMID: 26712813)
Grant Information: 326076 Norges Forskningsråd; The Norwegian Research Fund for Cancer in Dogs; Faculty of Veterinary Medicine, Norwegian University of Life Sciences
Contributed Indexing: Keywords: comparative study; dogs; gene expression profiling; mammary neoplasm; veterinary oncology
Entry Date(s): Date Created: 20260416 Date Completed: 20260810 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13456593
DOI: 10.1111/vco.70067
PMID: 41992075
Βάση Δεδομένων: MEDLINE
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  Data: Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes.
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  Data: <searchLink fieldCode="AU" term="%22Moberg+IM%22">Moberg IM</searchLink>; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.<br /><searchLink fieldCode="AU" term="%22Hansen+N%22">Hansen N</searchLink>; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.<br /><searchLink fieldCode="AU" term="%22Bergholtz+H%22">Bergholtz H</searchLink>; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.<br /><searchLink fieldCode="AU" term="%22Borge+KS%22">Borge KS</searchLink>; LINK Medical Research AS, Oslo, Norway.<br /><searchLink fieldCode="AU" term="%22Gunnes+G%22">Gunnes G</searchLink>; Pathology Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.<br /><searchLink fieldCode="AU" term="%22Arnet+EF%22">Arnet EF</searchLink>; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.<br /><searchLink fieldCode="AU" term="%22Guttersrud+OA%22">Guttersrud OA</searchLink>; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.<br /><searchLink fieldCode="AU" term="%22Solbakken+MH%22">Solbakken MH</searchLink>; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.<br /><searchLink fieldCode="AU" term="%22Lingaas+F%22">Lingaas F</searchLink>; Medical Genetics Unit, Department of Preclinical Sciences and Pathology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, Norway.
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  Data: <searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal%22">Mammary Neoplasms, Animal*</searchLink>/<searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal%22">Mammary Neoplasms, Animal*</searchLink>/<searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal%22">Mammary Neoplasms, Animal*</searchLink>/<searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal+classification%22">classification</searchLink> <br /><searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal%22">Mammary Neoplasms, Animal*</searchLink>/<searchLink fieldCode="MM" term="%22Mammary+Neoplasms%2C+Animal+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Dog+Diseases%22">Dog Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Dog+Diseases+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Dog+Diseases%22">Dog Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Dog+Diseases+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Dog+Diseases%22">Dog Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Dog+Diseases+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Dog+Diseases%22">Dog Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Dog+Diseases+classification%22">classification</searchLink> <br /><searchLink fieldCode="MM" term="%22Gene+Expression+Profiling%22">Gene Expression Profiling*</searchLink>/<searchLink fieldCode="MM" term="%22Gene+Expression+Profiling+veterinary%22">veterinary</searchLink> <br /><searchLink fieldCode="MM" term="%22Transcriptome%22">Transcriptome*</searchLink><br /><searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Dogs%22">Dogs</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Gene+Expression+Regulation%2C+Neoplastic%22">Gene Expression Regulation, Neoplastic</searchLink>
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  Label: Abstract
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  Data: This study presents a comprehensive transcriptomic analysis of 128 canine mammary tumours (CMTs), aiming to characterize their molecular landscape. Differential gene expression analysis (DGE), gene set enrichment analysis (GSEA) and clustering based on the human PAM50 gene panel were applied to explore molecular differences between the different histological categories. The analysis revealed transcriptomic differences between benign and malignant tumours as well as between tumours with high and low mitotic count. Malignant tumours were significantly enriched for gene sets associated with cell cycle regulation, proliferation, inflammatory response, signalling pathways and metabolic processes. Of the malignant tumours, purely epithelial tumours were enriched in gene sets related to proliferation, signalling and metabolic processes when compared to mixed tumours harbouring myoepithelial or mesenchymal components. To assess the relevance of human classification systems, CMTs were clustered on the PAM50 genes. The analysis revealed two clusters resembling human basal-like and luminal A subtypes, while the remaining tumours did not display expression patterns similar to human breast cancer subtypes. This suggests that there are limitations to applying the human molecular classification systems to canine tumours without adaptation. Additionally, CMTs displayed intragroup heterogeneity, where not all tumours within a histopathological category clustered together, indicating that the molecular aspect of CMTs is not necessarily reflected in the pathology. Together, this study highlights the need to develop canine-specific molecular markers based on gene expression, which could enable diagnosis prior to surgical removal of tumours, and ultimately improve treatment strategies and outcomes for dogs with mammary tumours.<br /> (© 2026 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)
– Name: Ref
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  Data: Vet Comp Oncol. 2009 Sep;7(3):162-72. (PMID: <searchLink fieldCode="PM" term="%2219691645%22">19691645)</searchLink><br />J Reprod Fertil Suppl. 2001;57:439-43. (PMID: <searchLink fieldCode="PM" term="%2211787188%22">11787188)</searchLink><br />Genome Biol. 2014;15(12):550. (PMID: <searchLink fieldCode="PM" term="%2225516281%22">25516281)</searchLink><br />Animals (Basel). 2021 Jul 12;11(7):. (PMID: <searchLink fieldCode="PM" term="%2234359206%22">34359206)</searchLink><br />Vet Pathol. 2020 Nov;57(6):774-790. (PMID: <searchLink fieldCode="PM" term="%2232807036%22">32807036)</searchLink><br />J Clin Oncol. 2009 Mar 10;27(8):1160-7. (PMID: <searchLink fieldCode="PM" term="%2219204204%22">19204204)</searchLink><br />Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: <searchLink fieldCode="PM" term="%2216199517%22">16199517)</searchLink><br />J Mammary Gland Biol Neoplasia. 2022 Jun;27(2):171-183. (PMID: <searchLink fieldCode="PM" term="%2235932380%22">35932380)</searchLink><br />Biomed Pharmacother. 2023 Jul;163:114822. (PMID: <searchLink fieldCode="PM" term="%2237146418%22">37146418)</searchLink><br />ISRN Oncol. 2012;2012:450267. (PMID: <searchLink fieldCode="PM" term="%2223227362%22">23227362)</searchLink><br />J Coll Physicians Surg Pak. 2018 Oct;28(10):783-790. (PMID: <searchLink fieldCode="PM" term="%2230266125%22">30266125)</searchLink><br />Nucleic Acids Res. 2025 Jan 11;53(2):. (PMID: <searchLink fieldCode="PM" term="%2239844453%22">39844453)</searchLink><br />Bioinformatics. 2014 Mar 15;30(6):801-7. (PMID: <searchLink fieldCode="PM" term="%2222321699%22">22321699)</searchLink><br />Biofilm. 2021 Jan 13;3:100043. (PMID: <searchLink fieldCode="PM" term="%2233665610%22">33665610)</searchLink><br />PLoS One. 2015 May 08;10(5):e0126371. (PMID: <searchLink fieldCode="PM" term="%2225955013%22">25955013)</searchLink><br />Vet Rec. 2010 May 8;166(19):586-90. (PMID: <searchLink fieldCode="PM" term="%2220453236%22">20453236)</searchLink><br />JCO Precis Oncol. 2017 Jul;2017:. (PMID: <searchLink fieldCode="PM" term="%2228890946%22">28890946)</searchLink><br />Nature. 2000 Aug 17;406(6797):747-52. (PMID: <searchLink fieldCode="PM" term="%2210963602%22">10963602)</searchLink><br />Vet Pathol. 2024 Sep;61(5):752-764. (PMID: <searchLink fieldCode="PM" term="%2238533804%22">38533804)</searchLink><br />Imeta. 2022 Aug 01;1(3):e43. (PMID: <searchLink fieldCode="PM" term="%2238868715%22">38868715)</searchLink><br />Front Oncol. 2020 Apr 28;10:617. (PMID: <searchLink fieldCode="PM" term="%2232411603%22">32411603)</searchLink><br />Vet Pathol. 2013 Jan;50(1):94-105. (PMID: <searchLink fieldCode="PM" term="%2222688585%22">22688585)</searchLink><br />Cell Syst. 2015 Dec 23;1(6):417-425. (PMID: <searchLink fieldCode="PM" term="%2226771021%22">26771021)</searchLink><br />Vet Sci. 2025 Feb 19;12(2):. (PMID: <searchLink fieldCode="PM" term="%2240005948%22">40005948)</searchLink><br />Nat Rev Genet. 2009 Jan;10(1):57-63. (PMID: <searchLink fieldCode="PM" term="%2219015660%22">19015660)</searchLink><br />Vet Med Int. 2024 May 10;2024:9319651. (PMID: <searchLink fieldCode="PM" term="%2238766503%22">38766503)</searchLink><br />Signal Transduct Target Ther. 2024 Aug 21;9(1):205. (PMID: <searchLink fieldCode="PM" term="%2239164274%22">39164274)</searchLink><br />Cancer Res. 2014 Sep 15;74(18):5045-56. (PMID: <searchLink fieldCode="PM" term="%2225082814%22">25082814)</searchLink><br />Vet Sci. 2023 May 30;10(6):. (PMID: <searchLink fieldCode="PM" term="%2237368765%22">37368765)</searchLink><br />Vet Pathol. 2011 Jan;48(1):117-31. (PMID: <searchLink fieldCode="PM" term="%2221266722%22">21266722)</searchLink><br />BMC Genomics. 2009 Mar 27;10:135. (PMID: <searchLink fieldCode="PM" term="%2219327144%22">19327144)</searchLink><br />Vet J. 2024 Feb;303:106055. (PMID: <searchLink fieldCode="PM" term="%2238097103%22">38097103)</searchLink><br />Cancer Discov. 2022 Jan;12(1):31-46. (PMID: <searchLink fieldCode="PM" term="%2235022204%22">35022204)</searchLink><br />Animals (Basel). 2023 Oct 09;13(19):. (PMID: <searchLink fieldCode="PM" term="%2237835752%22">37835752)</searchLink><br />Breast Cancer Res. 2023 Oct 3;25(1):114. (PMID: <searchLink fieldCode="PM" term="%2237789381%22">37789381)</searchLink><br />Vet Comp Oncol. 2026 Sep;24(3):444-457. (PMID: <searchLink fieldCode="PM" term="%2241992075%22">41992075)</searchLink><br />Brief Bioinform. 2021 Nov 5;22(6):. (PMID: <searchLink fieldCode="PM" term="%2234329375%22">34329375)</searchLink><br />PLoS One. 2021 Nov 22;16(11):e0260400. (PMID: <searchLink fieldCode="PM" term="%2234807950%22">34807950)</searchLink><br />Nat Commun. 2020 Mar 6;11(1):1234. (PMID: <searchLink fieldCode="PM" term="%2232144251%22">32144251)</searchLink><br />Nat Commun. 2020 Jul 17;11(1):3616. (PMID: <searchLink fieldCode="PM" term="%2232680987%22">32680987)</searchLink><br />Histopathology. 2023 Jan;82(1):5-16. (PMID: <searchLink fieldCode="PM" term="%2236482272%22">36482272)</searchLink><br />BMC Bioinformatics. 2016 Nov 25;17(1):483. (PMID: <searchLink fieldCode="PM" term="%2227884101%22">27884101)</searchLink><br />Vet Pathol. 2016 Jan;53(1):7-9. (PMID: <searchLink fieldCode="PM" term="%2226712813%22">26712813)</searchLink>
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      – SubjectFull: Mammary Neoplasms, Animal genetics
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      – TitleFull: Transcriptomic Profiling of Canine Mammary Tumours Reveals Significant Heterogeneity Between and Within Histological Classes.
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      – PersonEntity:
          Name:
            NameFull: Lingaas F
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 09
              Text: 2026 Sep
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1476-5829
          Numbering:
            – Type: volume
              Value: 24
            – Type: issue
              Value: 3
          Titles:
            – TitleFull: Veterinary and comparative oncology
              Type: main
ResultId 1