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

Nat Commun. 2020 Jul 17;11(1):3616. doi: 10.1038/s41467-020-17458-0.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Exome Sequencing
  • 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


  • Biomarkers, Tumor
  • Class I Phosphatidylinositol 3-Kinases