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基于阵列的基因组和表观基因组技术在揭示乳腺肿瘤异质性本质中的应用:迈向个体化治疗之路。

Application of array-based genomic and epigenomic technologies to unraveling the heterogeneous nature of breast tumors: on the road to individualized treatment.

作者信息

Abramovitz Mark, Leyland-Jones Brian

机构信息

VM Institute of Research, Montreal, Quebec, Canada.

出版信息

Cancer Genomics Proteomics. 2007 May-Jun;4(3):135-45.

Abstract

The recent application of genomic microarray technology to the molecular profiling of breast tumors has clearly demonstrated their heterogeneous nature. Targeted treatment strategies are having a clear impact on patient survival. It has also become apparent that accumulated mutations, genomic instability, epigenetic phenomena, genetic variability and environmental factors all contribute to the uniqueness of a patient's tumor. Novel genomic and epigenetic-based technologies have been or are being developed in order to greatly enhance the analysis of tumor samples including those samples previously thought unusable due to the fixation process, such as archival formalin-fixed paraffin-embedded (FFPE) samples. Patients and their tumors can now be studied with regard to genetic variation, genomic instability, gene expression, gene mutations, and methylation patterns. These areas of research are being made more accessible through genome-wide screening technologies and will, in the near future, rapidly expand our understanding of what contributes to the unique properties of each tumor and lead to the identification of genes that could be potential therapeutic targets for specific tumor subtypes. Application of these technologies to our understanding of breast cancer will undoubtedly have an impact on the individualization of treatment for breast cancer patients in the not to distant future.

摘要

基因组微阵列技术最近在乳腺肿瘤分子剖析中的应用清楚地表明了它们的异质性。靶向治疗策略对患者生存率产生了明显影响。同样明显的是,累积突变、基因组不稳定性、表观遗传现象、遗传变异性和环境因素都导致了患者肿瘤的独特性。新型基于基因组和表观遗传学的技术已经或正在被开发出来,以极大地加强对肿瘤样本的分析,包括那些由于固定过程而以前被认为无法使用的样本,如存档福尔马林固定石蜡包埋(FFPE)样本。现在可以对患者及其肿瘤进行基因变异、基因组不稳定性、基因表达、基因突变和甲基化模式方面的研究。通过全基因组筛选技术,这些研究领域正变得更容易进入,并且在不久的将来,将迅速扩展我们对导致每个肿瘤独特特性的因素的理解,并导致识别出可能成为特定肿瘤亚型潜在治疗靶点的基因。将这些技术应用于我们对乳腺癌的理解,无疑将在不久的将来对乳腺癌患者治疗的个体化产生影响。

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