原创力文档an integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer一个综合多维遗传和表观遗传策略来识别异常的基因和通路在癌症.pdfVIP
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an integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer一个综合多维遗传和表观遗传策略来识别异常的基因和通路在癌症
Chari et al. BMC Systems Biology 2010, 4:67
/1752-0509/4/67
R E S E A R C H A R T I C L E Open Access
Research article
An integrative multi-dimensional genetic and
epigenetic strategy to identify aberrant genes and
pathways in cancer
Raj Chari*, Bradley P Coe, Emily A Vucic, William W Lockwood and Wan L Lam
Abstract
Background: Genomics has substantially changed our approach to cancer research. Gene expression profiling, for
example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic
signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and
epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the
potential for large scale integration of genome and transcriptome data generated from a variety of technology
platforms to acquire a better understanding of cancer.
Results: Here we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms
that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in
a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption
(MCD) analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would
be overlooked in single genomic dimension investigations.
Conclusions: Notably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide
analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our
findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape
conventional single dimensional analysis and as such, reduce the c
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