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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  ;  Sangwoo Kim 
 NATURE COMMUNICATIONS, Vol.11(1) : 3616, 2020-07 
Journal Title
Issue Date
Animals ; Biomarkers, Tumor / genetics* ; Breast / pathology ; Breast Neoplasms / genetics* ; Breast Neoplasms / mortality ; Breast Neoplasms / pathology ; Carcinogenesis / genetics* ; Class I Phosphatidylinositol 3-Kinases / genetics ; Cohort Studies ; DNA Copy Number Variations ; DNA Mutational Analysis ; Datasets as Topic ; Dogs ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic* ; Humans ; Mammary Glands, Animal / pathology ; Mammary Glands, Animal / surgery ; Mammary Neoplasms, Animal / genetics* ; Mammary Neoplasms, Animal / mortality ; Mammary Neoplasms, Animal / pathology ; Mammary Neoplasms, Animal / surgery ; Mutation ; Prognosis ; RNA-Seq ; Species Specificity ; Whole Exome Sequencing
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.
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1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Kim, Hyun Seok(김현석) ORCID logo https://orcid.org/0000-0003-4498-8690
Yang, In Seok(양인석) ORCID logo https://orcid.org/0000-0001-5224-2587
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
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