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

杂合子丢失 生物 PTEN公司 拷贝数变化 癌症研究 基因剂量 恶性肿瘤 乳腺 癌症 病理 染色体不稳定性 乳腺癌 基因 遗传学 医学 染色体 基因组 等位基因 基因表达 PI3K/AKT/mTOR通路 信号转导
作者
Kaja Sverdrup Borge,Silje Nord,Peter Van Loo,Ole Christian Lingjærde,Gjermund Gunnes,Grethe I.G. Alnæs,Hiroko Kato Solvang,Torben Lüders,Vessela N. Kristensen,Anne‐Lise Børresen‐Dale,Frode Lingaas
出处
期刊:PLOS ONE [Public Library of Science]
卷期号:10 (5): e0126371-e0126371 被引量:31
标识
DOI:10.1371/journal.pone.0126371
摘要

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.
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