Canine Mammary Tumours Are Affected by Frequent Copy Number Aberrations, including Amplification of MYC and Loss of PTEN

PLoS One. 2015 May 8;10(5):e0126371. doi: 10.1371/journal.pone.0126371. eCollection 2015.

Abstract

Background: Copy number aberrations frequently occur during the development of many cancers. Such events affect dosage of involved genes and may cause further genomic instability and progression of cancer. In this survey, canine SNP microarrays were used to study 117 canine mammary tumours from 69 dogs.

Results: We found a high occurrence of copy number aberrations in canine mammary tumours, losses being more frequent than gains. Increased frequency of aberrations and loss of heterozygosity were positively correlated with increased malignancy in terms of histopathological diagnosis. One of the most highly recurrently amplified regions harbored the MYC gene. PTEN was located to a frequently lost region and also homozygously deleted in five tumours. Thus, deregulation of these genes due to copy number aberrations appears to be an important event in canine mammary tumour development. Other potential contributors to canine mammary tumour pathogenesis are COL9A3, INPP5A, CYP2E1 and RB1. The present study also shows that a more detailed analysis of chromosomal aberrations associated with histopathological parameters may aid in identifying specific genes associated with canine mammary tumour progression.

Conclusions: The high frequency of copy number aberrations is a prominent feature of canine mammary tumours as seen in other canine and human cancers. Our findings share several features with corresponding studies in human breast tumours and strengthen the dog as a suitable model organism for this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Chromosome Aberrations
  • Collagen Type IX / genetics
  • Comparative Genomic Hybridization
  • Cytochrome P-450 CYP2E1 / genetics
  • DNA Copy Number Variations
  • Dogs
  • Female
  • Humans
  • Inositol Polyphosphate 5-Phosphatases
  • Loss of Heterozygosity
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology*
  • PTEN Phosphohydrolase / genetics*
  • Phosphoric Monoester Hydrolases / genetics
  • Ploidies
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-myc / genetics*

Substances

  • Collagen Type IX
  • Proto-Oncogene Proteins c-myc
  • Cytochrome P-450 CYP2E1
  • Phosphoric Monoester Hydrolases
  • INPP5A protein, human
  • Inositol Polyphosphate 5-Phosphatases
  • PTEN Phosphohydrolase

Grants and funding

This work was (partly) funded by the European Commission (LUPA, GA-201370). The authors are grateful to “The research fund; Cancer in the dog”, “Astri og Birger Torsteds legat til fordel for dyrene”, the Legacy of Veterinary Edvard Smidt, and the Norwegian School of Veterinary Sciences for the financial contribution to this study. PVL is a postdoctoral researcher of the Research Foundation – Flanders (FWO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.