A pathway-based classification of human breast cancer

被引:265
作者
Gatza, Michael L. [1 ]
Lucas, Joseph E. [1 ,2 ]
Barry, William T. [1 ,3 ]
Kim, Jong Wook [1 ,4 ]
Wang, Quanli [1 ,2 ]
Crawford, Matthew D. [1 ]
Datto, Michael B. [5 ]
Kelley, Michael [6 ]
Mathey-Prevot, Bernard [1 ,7 ]
Potti, Anil [1 ,6 ]
Nevins, Joseph R. [1 ,4 ]
机构
[1] Duke Univ, Med Ctr, Duke Inst Genome Sci & Policy, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Stat Sci, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[6] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[7] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
cancer genomics; tumor subgroup; GENE-EXPRESSION DATA; MOLECULAR SUBTYPES; CARCINOMAS; IDENTIFICATION; SIGNATURE; ERLOTINIB; CETUXIMAB; PATTERNS; STRATEGY; RESPOND;
D O I
10.1073/pnas.0912708107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:6994 / 6999
页数:6
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