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