title: Canine Mammary Tumours Are Affected by Frequent Copy Number Aberrations, including Amplification of MYC and Loss of PTEN.
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.
authors.affiliation: Section of Genetics, Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU),Oslo, Norway.
authors.forename: Kaja S
authors.initials: KS
authors.lastname: Borge
authors.affiliation: Department of Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Silje
authors.initials: S
authors.lastname: Nord
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; Human Genome Laboratory, Department of Human Genetics, VIB and University of Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Van Loo
authors.affiliation: Department of Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Radiumhospitalet, Oslo, Norway; Biomedical Informatics, Department of Informatics, University of Oslo, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: Ole C
authors.initials: OC
authors.lastname: Lingjærde
authors.affiliation: Section of Anatomy and Pathology, Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), Oslo, Norway.
authors.forename: Gjermund
authors.initials: G
authors.lastname: Gunnes
authors.affiliation: Department of Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Grethe I G
authors.initials: GI
authors.lastname: Alnæs
authors.affiliation: Marine Mammals Research Group, Institute of Marine Research, Bergen, Norway.
authors.forename: Hiroko K
authors.initials: HK
authors.lastname: Solvang
authors.affiliation: Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Akershus University Hospital, Lørenskog, Norway.
authors.forename: Torben
authors.initials: T
authors.lastname: Lüders
authors.affiliation: Department of Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Radiumhospitalet, Oslo, Norway; The K. G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology, Division of Medicine, Akershus University Hospital, Ahus, Norway.
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
authors.affiliation: Department of Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Radiumhospitalet, Oslo, Norway; The K. G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Section of Genetics, Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU),Oslo, Norway.
authors.forename: Frode
authors.initials: F
authors.lastname: Lingaas
mesh_terms: D000483:Alleles; D000818:Animals; D002869:Chromosome Aberrations; D024081:Collagen Type IX / Q000235:genetics; D055028:Comparative Genomic Hybridization; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D056915:DNA Copy Number Variations; D004285:Dogs; D005260:Female; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D019656:Loss of Heterozygosity; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011003:Ploidies; D020641:Polymorphism, Single Nucleotide; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
chemical_list: D024081:Collagen Type IX; D016271:Proto-Oncogene Proteins c-myc; D019392:Cytochrome P-450 CYP2E1; D010744:Phosphoric Monoester Hydrolases; C000606429:INPP5A protein, human; D000072181:Inositol Polyphosphate 5-Phosphatases; D051059:PTEN Phosphohydrolase