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WIREs Syst Biol Med
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Genomics and epigenomics of colorectal cancer

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Abstract Colorectal cancer is one of the most common cancer types worldwide and accounts for approximately 600,000 deaths annually. Work over the last decades has uncovered a number of tumor‐suppressor and oncogenes which are frequently mutated and might thus be responsible for the malignant transformation. However, only with the development of new high‐throughput technologies systematic analyses of the genome and epigenomes became feasible. While data generation has increased exponential, we are now faced with new challenges to transform these data into useful models that help predicting the outcome of genomic aberrations and to develop novel diagnostic and therapeutic strategies. As a basis for the modeling it is essential to understand and integrate current knowledge. We review previous and current ideas in colorectal cancer development and focus on a pathway oriented view. We show that colorectal cancer is a multilayer complex disease affecting the genome as well as the epigenome with direct consequences on the gene and microRNA (miRNA) expression signatures. The goal is to illustrate the current principles of colorectal cancer pathogenesis and to illustrate the need for elaborate computer modeling systems. WIREs Syst Biol Med 2013, 5:205–219. doi: 10.1002/wsbm.1206 This article is categorized under: Analytical and Computational Methods > Analytical Methods Laboratory Methods and Technologies > Genetic/Genomic Methods Translational, Genomic, and Systems Medicine > Therapeutic Methods Translational, Genomic, and Systems Medicine > Translational Medicine

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Model of the colorectal cancer network. The role of miRNAs and mutations in colorectal cancer (CRC) pathogenesis. Selected miRNAs along with their targets are indicated. Mutations are derived from recent high‐throughput studies. Filled circle: Wood et al.39; circle: Sjoblom et al.38; star: Timmermann et al.32; cross: Bass et al.14; triangle: TCGA. ECM, extracellular matrix; EMT, epithelial‐to‐mesenchymal transition; ICAM, intercellular adhesive molecules; MMP, matrix metallopeptidase. (Reprinted with permission from Refs 10, 89, and 90)

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