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利用单核苷酸多态性(SNP)基因分型分析对犬乳腺肿瘤全基因组结构畸变进行表征。

Characterisation of genome-wide structural aberrations in canine mammary tumours using single nucleotide polymorphism (SNP) genotyping assay.

作者信息

Surdyka M, Gurgul A, Slaska B, Pawlina K, Szmatola T, Bugno-Poniewierska M, Smiech A, Kasperek K

机构信息

Institute of Biological Bases of Animal Production, Faculty of Biology, Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland.

Department of Animal Breeding and Genetics, National Research Institute of Animal Production in Balice, Krakowska 1, 32-083 Balice, Poland.

出版信息

Pol J Vet Sci. 2019 Mar;22(1):133-141. doi: 10.24425/pjvs.2019.127080.

Abstract

Characterisation of copy number variation (CNV) and loss of heterozygosity (LOH) has pro- vided evidence for the relationship of this type of genetic variation with the occurrence of a broad spectrum of diseases, including cancer lesions. The role of CNVs and germinal or somatic LOHs in canine mammary tumours is still unknown. Therefore, the aim of this study was to identify CNVs and LOHs in canine mammary tumours. Forty-eight samples obtained from normal (n=24) and tumour (n=24) tissues of dogs were analysed. In the study, we used CanineHD BeadChip assay (Illumina) and OncoSNP software to identify copy number alternations in genomes of dif- ferent dog breeds and in different mammary cancer types occurring in this species. The analyses revealed that, in the case of CNV, the amplification-type variants were longer and more frequent than deletions. Based on the analysis of the frequency of different types of aberrations in the in- dividual parts of the genome, regions that are particularly susceptible to structural aberrations were indicated. The fraction of genes identified within these regions was associated with major processes of neoplastic transformation. Association analysis of such traits as tumour grading as well as the size and age of dogs demonstrated that structural aberrations were more frequent in dogs diagnosed with tumour malignancy grade II and III, in dogs with a larger body size, and in large dogs aged 7-8. The promising results of these pioneering investigations prompt continuation thereof to analyse other types of cancer.

摘要

拷贝数变异(CNV)和杂合性缺失(LOH)的特征分析为这类基因变异与包括癌症病变在内的多种疾病发生之间的关系提供了证据。CNV以及生殖系或体细胞LOH在犬乳腺肿瘤中的作用仍不清楚。因此,本研究的目的是鉴定犬乳腺肿瘤中的CNV和LOH。对从犬的正常组织(n = 24)和肿瘤组织(n = 24)中获取的48个样本进行了分析。在本研究中,我们使用犬类HD BeadChip检测法(Illumina公司)和OncoSNP软件来鉴定不同犬种以及该物种中出现的不同类型乳腺癌基因组中的拷贝数变化。分析显示,就CNV而言,扩增型变异比缺失型变异更长且更频繁。基于对基因组各个部分不同类型畸变频率的分析,指出了特别容易发生结构畸变的区域。在这些区域内鉴定出的基因部分与肿瘤转化的主要过程相关。对肿瘤分级以及犬的体型和年龄等特征进行的关联分析表明,在诊断为肿瘤恶性程度II级和III级的犬、体型较大的犬以及7 - 8岁的大型犬中,结构畸变更为频繁。这些开创性研究的良好结果促使继续开展研究以分析其他类型的癌症。

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