Borge Kaja S, Nord Silje, Van Loo Peter, Lingjærde Ole C, Gunnes Gjermund, Alnæs Grethe I G, Solvang Hiroko K, Lüders Torben, Kristensen Vessela N, Børresen-Dale Anne-Lise, Lingaas Frode
Section of Genetics, Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU),Oslo, Norway.
Department of Genetics, Institute for Cancer Research, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
PLoS One. 2015 May 8;10(5):e0126371. doi: 10.1371/journal.pone.0126371. eCollection 2015.
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.
在许多癌症的发展过程中，拷贝数畸变经常发生。此类事件会影响相关基因的剂量，并可能导致进一步的基因组不稳定和癌症进展。在本研究中，犬类单核苷酸多态性微阵列被用于研究来自69只犬的117个犬乳腺肿瘤。
我们发现犬乳腺肿瘤中拷贝数畸变的发生率很高，缺失比增加更为常见。从组织病理学诊断来看，畸变频率的增加和杂合性缺失与恶性程度的增加呈正相关。其中一个高度反复扩增的区域包含MYC基因。PTEN定位于一个经常缺失的区域，并且在五个肿瘤中呈纯合缺失。因此，由于拷贝数畸变导致这些基因的失调似乎是犬乳腺肿瘤发展中的一个重要事件。犬乳腺肿瘤发病机制的其他潜在因素包括COL9A3、INPP5A、CYP2E1和RB1。本研究还表明，对与组织病理学参数相关的染色体畸变进行更详细的分析可能有助于识别与犬乳腺肿瘤进展相关的特定基因。
拷贝数畸变的高频率是犬乳腺肿瘤的一个突出特征，这在其他犬类和人类癌症中也有体现。我们的发现与人类乳腺肿瘤的相应研究有几个共同特征，并强化了犬作为这种疾病合适模型生物的地位。
