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犬和人乳腺肿瘤的分子生物学方面。

Molecular biological aspects on canine and human mammary tumors.

机构信息

Center of Clinical Comparative Oncology C3O, Department of Clinical Sciences, Division of Small Animals, Swedish University of Agricultural Sciences, PO Box 7054, S-750 07, Uppsala, Sweden.

出版信息

Vet Pathol. 2011 Jan;48(1):132-46. doi: 10.1177/0300985810387939. Epub 2010 Dec 7.

Abstract

The high incidence of mammary tumor disease reported in certain canine breeds suggests a significant genetic component, as has already been described in human familial breast cancer-in BRCA1- and BRCA2-associated breast cancer in particular. The identification of genetic risk factors is critical to improvements in the prevention, diagnosis, and treatment of these tumors. In recent years, there has been significant progress in developing the tools and reagents necessary to analyze the canine genome. This work has culminated in a high-quality draft genome sequence, as well as a single-nucleotide polymorphism map and single-nucleotide polymorphism arrays for genomewide association analysis. These tools provide an unprecedented opportunity to characterize the genetic influences in canine diseases such as cancer, eventually allowing for exploration of more effective therapies. Given the high homology between the canine genome sequence and its human counterpart--as well as the many similarities regarding the morphology, biological behavior, and clinical course of mammary tumors in both species--the dog has proven to be an excellent comparative model. This review highlights the comparative aspects regarding certain areas within molecular biology, and it discusses future perspectives. The findings in larger genomewide association analyses and cDNA expression arrays are described, and the BRCA1/BRCA2 complex is compared in detail between the 2 species.

摘要

某些犬种报告的乳腺肿瘤疾病高发率表明存在显著的遗传因素,这与人类家族性乳腺癌中已经描述的 BRCA1 和 BRCA2 相关乳腺癌相似。确定遗传风险因素对于改善这些肿瘤的预防、诊断和治疗至关重要。近年来,在开发分析犬基因组所需的工具和试剂方面取得了重大进展。这项工作的最终成果是获得了高质量的基因组草图序列,以及单核苷酸多态性图谱和全基因组关联分析的单核苷酸多态性芯片。这些工具为研究癌症等犬科疾病的遗传影响提供了前所未有的机会,最终可以探索更有效的治疗方法。鉴于犬基因组序列与其人类对应物之间的高度同源性,以及这两个物种的乳腺肿瘤在形态、生物学行为和临床过程方面的许多相似性,犬已被证明是一种出色的比较模型。这篇综述强调了分子生物学某些领域的比较方面,并讨论了未来的展望。描述了更大规模的全基因组关联分析和 cDNA 表达芯片的结果,并详细比较了这两个物种的 BRCA1/BRCA2 复合物。

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