PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia
Abstract Biological features of neoplastic disease affecting mammary gland tissue are shared between canines and humans. Research performed in either species has translational value and early phase clinical trials performed in canines with spontaneous disease could be informative for human trials. T...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-27664-7 |
| _version_ | 1797952548819173376 |
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| author | Maja Louise Arendt Sharadha Sakthikumar Malin Melin Ingegerd Elvers Patricio Rivera Majbritt Larsen Sara Saellström Frode Lingaas Henrik Rönnberg Kerstin Lindblad-Toh |
| author_facet | Maja Louise Arendt Sharadha Sakthikumar Malin Melin Ingegerd Elvers Patricio Rivera Majbritt Larsen Sara Saellström Frode Lingaas Henrik Rönnberg Kerstin Lindblad-Toh |
| author_sort | Maja Louise Arendt |
| collection | DOAJ |
| description | Abstract Biological features of neoplastic disease affecting mammary gland tissue are shared between canines and humans. Research performed in either species has translational value and early phase clinical trials performed in canines with spontaneous disease could be informative for human trials. The purpose of this study was to investigate the somatic genetic aberrations occurring in canine mammary neoplasia by exome capture and next generation sequencing. Based on 55 tumor-normal pairs we identified the PIK3CA gene as the most commonly mutated gene in canine mammary tumors, with 25% of samples carrying mutations in this gene. A recurrent missense mutation was identified, p.H1047R, which is homologous to the human PIK3CA hotspot mutation found in different types of breast neoplasia. Mutations homologous to other known human mutation hotspots such as the PIK3CA p.E545K and the KRAS p.G12V/D were also identified. We identified copy number aberrations affecting important tumor suppressor and oncogenic pathways including deletions affecting the PTEN tumor suppressor gene. We suggest that activation of the KRAS or PIK3CA oncogenes or loss of the PTEN suppressor gene may be important for mammary tumor development in dogs. This data endorses the conservation of cancer across species and the validity of studying cancer in non-human species. |
| first_indexed | 2024-04-10T22:49:19Z |
| format | Article |
| id | doaj.art-62ae4238724a400db3cc8b65801a96f2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T22:49:19Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-62ae4238724a400db3cc8b65801a96f22023-01-15T12:08:48ZengNature PortfolioScientific Reports2045-23222023-01-011311810.1038/s41598-023-27664-7PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasiaMaja Louise Arendt0Sharadha Sakthikumar1Malin Melin2Ingegerd Elvers3Patricio Rivera4Majbritt Larsen5Sara Saellström6Frode Lingaas7Henrik Rönnberg8Kerstin Lindblad-Toh9Department of Veterinary Clinical Sciences, University of CopenhagenBroad Institute of MIT and HarvardScience for Life Laboratory, Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Uppsala UniversityKarolinska HospitalVettris SundsvallEvidensia Specialist HospitalSwedish University of Agricultural SciencesVeterinary Faculty, Norwegian University of Life SciencesSwedish University of Agricultural SciencesScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala UniversityAbstract Biological features of neoplastic disease affecting mammary gland tissue are shared between canines and humans. Research performed in either species has translational value and early phase clinical trials performed in canines with spontaneous disease could be informative for human trials. The purpose of this study was to investigate the somatic genetic aberrations occurring in canine mammary neoplasia by exome capture and next generation sequencing. Based on 55 tumor-normal pairs we identified the PIK3CA gene as the most commonly mutated gene in canine mammary tumors, with 25% of samples carrying mutations in this gene. A recurrent missense mutation was identified, p.H1047R, which is homologous to the human PIK3CA hotspot mutation found in different types of breast neoplasia. Mutations homologous to other known human mutation hotspots such as the PIK3CA p.E545K and the KRAS p.G12V/D were also identified. We identified copy number aberrations affecting important tumor suppressor and oncogenic pathways including deletions affecting the PTEN tumor suppressor gene. We suggest that activation of the KRAS or PIK3CA oncogenes or loss of the PTEN suppressor gene may be important for mammary tumor development in dogs. This data endorses the conservation of cancer across species and the validity of studying cancer in non-human species.https://doi.org/10.1038/s41598-023-27664-7 |
| spellingShingle | Maja Louise Arendt Sharadha Sakthikumar Malin Melin Ingegerd Elvers Patricio Rivera Majbritt Larsen Sara Saellström Frode Lingaas Henrik Rönnberg Kerstin Lindblad-Toh PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia Scientific Reports |
| title | PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia |
| title_full | PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia |
| title_fullStr | PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia |
| title_full_unstemmed | PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia |
| title_short | PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia |
| title_sort | pik3ca is recurrently mutated in canine mammary tumors similarly to in human mammary neoplasia |
| url | https://doi.org/10.1038/s41598-023-27664-7 |
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