Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer

Deli Liu, Huan Xiong, Angela E. Ellis, Nicole C. Northrup, Carlos O. Rodriguez, Ruth M. O'Regan, Stephen Dalton, Shaying Zhao

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Spontaneously occurring canine mammary cancer represents an excellent model of human breast cancer, but is greatly understudied. To better use this valuable resource, we performed whole-genome sequencing, whole-exome sequencing, RNA-seq, and/or high-density arrays on twelve canine mammary cancer cases, including seven simple carcinomas and four complex carcinomas. Canine simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many of which faithfully recapitulate key features of human breast cancer. Canine complex carcinomas, which are characterized by proliferation of both luminal and myoepithelial cells and are rare in human breast cancer, seem to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated and are abnormally enriched with active histone modification H4-acetylation, whereas aberrantly depleted with repressive histone modification H3K9me3. Our findings indicate the likelihood that canine simple carcinomas arise from genomic aberrations, whereas complex carcinomas originate from epigenomic alterations, reinforcing their unique value. Canine complex carcinomas offer an ideal system to study myoepithelial cells, the second major cell lineage of the mammary gland. Canine simple carcinomas, which faithfully represent human breast carcinomas at the molecular level, provide indispensable models for basic and translational breast cancer research.

Original languageEnglish (US)
Pages (from-to)5045-5056
Number of pages12
JournalCancer Research
Volume74
Issue number18
DOIs
StatePublished - Jul 31 2014

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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    Liu, D., Xiong, H., Ellis, A. E., Northrup, N. C., Rodriguez, C. O., O'Regan, R. M., Dalton, S., & Zhao, S. (2014). Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer. Cancer Research, 74(18), 5045-5056. https://doi.org/10.1158/0008-5472.CAN-14-0392