Cross-species oncogenic signatures of breast cancer in canine mammary tumors

Tae-Min Kim, In Seok Yang, Byung-Joon Seung, Sejoon Lee, Dohyun Kim, Yoo-Jin Ha, Mi-kyoung Seo, Ka-Kyung Kim, Hyun Seok Kim, Jae-Ho Cheong, Jung-Hyang Sur, Hojung Nam and Sangwoo Kim ()
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Tae-Min Kim: The Catholic University of Korea
In Seok Yang: Yonsei University College of Medicine
Byung-Joon Seung: Konkuk University
Sejoon Lee: Seoul National University Bundang Hospital
Dohyun Kim: Gwangju Institute of Science and Technology (GIST)
Yoo-Jin Ha: Yonsei University College of Medicine
Mi-kyoung Seo: Yonsei University College of Medicine
Ka-Kyung Kim: Yonsei University College of Medicine
Hyun Seok Kim: Yonsei University College of Medicine
Jae-Ho Cheong: Yonsei University College of Medicine
Jung-Hyang Sur: Konkuk University
Hojung Nam: Gwangju Institute of Science and Technology (GIST)
Sangwoo Kim: Yonsei University College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Genomic and precision medicine research has afforded notable advances in human cancer treatment, yet applicability to other species remains uncertain. Through whole-exome and transcriptome analyses of 191 spontaneous canine mammary tumors (CMTs) that exhibit the archetypal features of human breast cancers, we found a striking resemblance of genomic characteristics including frequent PIK3CA mutations (43.1%), aberrations of the PI3K-Akt pathway (61.7%), and key genes involved in cancer initiation and progression. We also identified three gene expression-based CMT subtypes, one of which segregated with basal-like human breast cancer subtypes with activated epithelial-to-mesenchymal transition, low claudin expression, and unfavorable disease prognosis. A relative lack of ERBB2 amplification and Her2-enrichment subtype in CMT denoted species-specific molecular mechanisms. Taken together, our results elucidate cross-species oncogenic signatures for a better understanding of universal and context-dependent mechanisms in breast cancer development and provide a basis for precision diagnostics and therapeutics for domestic dogs.

Date: 2020
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DOI: 10.1038/s41467-020-17458-0

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