Journal Article

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

Lingjærde, Ole Christian, Alnæs, Grethe I Grenaker, Lingaas, Frode, Kristensen, Vessela N, Van Loo, Peter, Solvang, Hiroko Kato, Børresen-Dale, Anne-Lise, Luders, Torben, Gunnes, Gjermund, Nord, Silje, Borge, Kaja Sverdrup

2015

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aberration / Alleles / Animals / Breast cancer / Breast tumors / Cancer / Chromosome Aberrations / Clinical medicine / Collagen (type IX) / Collagen Type IX - genetics / Comparative Genomic Hybridization / Copy number / Cytochrome / Cytochrome P-450 CYP2E1 - genetics / Deoxyribonucleic acid / Deregulation / DNA / DNA Copy Number Variations / DNA microarrays / Dog diseases / Dogs / Female / Gene amplification / Genes / Genetic aspects / Genetic variation / Genetics / Genomic instability / Heterozygosity / Humans / Informatics / Inositol Polyphosphate 5-Phosphatases / Laboratories / Life sciences / Loss of Heterozygosity / Malignancy / Mammary Neoplasms, Animal - metabolism / Mammary Neoplasms, Animal - pathology / Medical diagnosis / Medical prognosis / Medical research / Molecular biology / Myc protein / Parameter identification / Pathogenesis / Phosphoric Monoester Hydrolases - genetics / Physiological aspects / Ploidies / Polymorphism, Single Nucleotide / Proto-Oncogene Proteins c-myc - genetics / PTEN Phosphohydrolase - genetics / PTEN protein / Risk factors / Single-nucleotide polymorphism / Stability / Studies / Surgery / Tumors / Veterinary medicine