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PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia.
Arendt, Maja Louise; Sakthikumar, Sharadha; Melin, Malin; Elvers, Ingegerd; Rivera, Patricio; Larsen, Majbritt; Saellström, Sara; Lingaas, Frode; Rönnberg, Henrik; Lindblad-Toh, Kerstin.
Afiliación
  • Arendt ML; Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark. maja.arendt@sund.ku.dk.
  • Sakthikumar S; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. maja.arendt@sund.ku.dk.
  • Melin M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Elvers I; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Clinical Genomics Uppsala, Uppsala University, Uppsala, Sweden.
  • Rivera P; Karolinska Hospital, Stockholm, Sweden.
  • Larsen M; Vettris Sundsvall, Sundsvall, Sweden.
  • Saellström S; Evidensia Specialist Hospital, Helsingborg, Sweden.
  • Lingaas F; Swedish University of Agricultural Sciences, Uppsala, Sweden.
  • Rönnberg H; Veterinary Faculty, Norwegian University of Life Sciences, Ås, Norway.
  • Lindblad-Toh K; Swedish University of Agricultural Sciences, Uppsala, Sweden.
Sci Rep ; 13(1): 632, 2023 01 12.
Article en En | MEDLINE | ID: mdl-36635367
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Mamarias Animales / Fosfatidilinositol 3-Quinasa Clase I Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Mamarias Animales / Fosfatidilinositol 3-Quinasa Clase I Límite: Animals / Female / Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido