Canine mammary tumours are affected by frequent copy number aberrations, including amplification of MYC and loss of PTEN

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 ...Background: 拷贝数变异（Copy number aberrations）在多种癌症的发生发展进程中频繁发生。此类事件会影响其所涉及基因的剂量，并可能引发进一步的基因组不稳定及癌症进展。本研究采用犬类单核苷酸多态性微阵列（canine SNP microarrays），对来自69只犬的117例犬乳腺肿瘤展开了研究。 Results: 本研究发现，犬乳腺肿瘤中拷贝数变异的发生率较高，其中拷贝数缺失的发生频率高于拷贝数增加。经组织病理学诊断可知，变异频率与杂合性缺失（loss of heterozygosity）的升高与肿瘤恶性程度的提升呈正相关。在最频繁出现的扩增区域中，有一个区域包含MYC基因。PTEN基因位于一个频繁发生缺失的区域内，且在5例肿瘤中发生了纯合缺失。由此可见，由拷贝数变异导致的上述基因表达失调，是犬乳腺肿瘤发生发展过程中的重要事件。其他可能参与犬乳腺肿瘤发病机制的潜在基因包括COL9A3、INPP5A、CYP2E1及RB1。……