PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia
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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.
In: Scientific Reports, Vol. 13, 632, 12.01.2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - PIK3CA is recurrently mutated in canine mammary tumors, similarly to in human mammary neoplasia
AU - Arendt, Maja Louise
AU - Sakthikumar, Sharadha
AU - Melin, Malin
AU - Elvers, Ingegerd
AU - Rivera, Patricio
AU - Larsen, Majbritt
AU - Saellström, Sara
AU - Lingaas, Frode
AU - Rönnberg, Henrik
AU - Lindblad-Toh, Kerstin
N1 - © 2023. The Author(s).
PY - 2023/1/12
Y1 - 2023/1/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-023-27664-7
DO - 10.1038/s41598-023-27664-7
M3 - Journal article
C2 - 36635367
VL - 13
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 632
ER -
ID: 333046067