A pathway-based classification of human breast cancer
A pathway-based classification of human breast cancer
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DOI：
10.1073/pnas.0912708107
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发表时间：
2010-04-13
影响因子：
11.1
通讯作者：
Nevins, Joseph R.
中科院分区：
文献类型：
--
作者：
Gatza, Michael L.;Lucas, Joseph E.;Nevins, Joseph R.
人类癌症的特点是异质性，反映了在肿瘤发生过程中获得的大量体细胞突变的复杂性和可变性。分析这种异质性，识别代表疾病共同机制的亚群，对于理解遗传改变的复杂性和提供制定合理治疗策略的框架至关重要。在这里，我们描述了一个人类乳腺癌的分类方案，利用途径活动的模式，建立在以前的亚型特征的基础上，使用内在的基因表达特征，提供基因表达数据的功能解释，可以与治疗方案联系起来。我们表明，鉴定出的亚群提供了一个强大的机制，用于分类独立样本，鉴定共享通路活性模式并表现出相似临床和生物学特性的肿瘤，包括在异质肿瘤总体中不明显的染色体改变的不同模式。我们建议，这种分类方案为理解引起这些肿瘤的复杂肿瘤发生机制和确定合理的联合治疗机会提供了基础。
The hallmark of human cancer is heterogeneity, reflecting the complexity and variability of the vast array of somatic mutations acquired during oncogenesis. An ability to dissect this heterogeneity, to identify subgroups that represent common mechanisms of disease, will be critical to understanding the complexities of genetic alterations and to provide a framework to develop rational therapeutic strategies. Here, we describe a classification scheme for human breast cancer making use of patterns of pathway activity to build on previous subtype characterizations using intrinsic gene expression signatures, to provide a functional interpretation of the gene expression data that can be linked to therapeutic options. We show that the identified subgroups provide a robust mechanism for classifying independent samples, identifying tumors that share patterns of pathway activity and exhibit similar clinical and biological properties, including distinct patterns of chromosomal alterations that were not evident in the heterogeneous total population of tumors. We propose that this classification scheme provides a basis for understanding the complex mechanisms of oncogenesis that give rise to these tumors and to identify rational opportunities for combination therapies.