Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues |
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Authors: | Francisco Sánchez-Vega Valer Gotea Hanna M Petrykowska Gennady Margolin Thomas C Krivak Julie A DeLoia Daphne W Bell Laura Elnitski |
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Affiliation: | 1.Genome Technology Branch; National Human Genome Research Institute; National Institutes of Health; Bethesda, MD USA;2.Department of Obstetrics, Gynecology and Reproductive Sciences; University of Pittsburgh Medical School; Pittsburgh, PA USA;3.School of Public Health and Health Services; The George Washington University; Washington DC, USA;4.Cancer Genetics Branch; National Human Genome Research Institute; National Institutes of Health; Bethesda, MD USA |
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Abstract: | Aberrant DNA methylation often occurs in colorectal cancer (CRC). In our study we applied a genome-wide DNA methylation analysis approach, MethylCap-seq, to map the differentially methylated regions (DMRs) in 24 tumors and matched normal colon samples. In total, 2687 frequently hypermethylated and 468 frequently hypomethylated regions were identified, which include potential biomarkers for CRC diagnosis. Hypermethylation in the tumor samples was enriched at CpG islands and gene promoters, while hypomethylation was distributed throughout the genome. Using epigenetic data from human embryonic stem cells, we show that frequently hypermethylated regions coincide with bivalent loci in human embryonic stem cells. DNA methylation is commonly thought to lead to gene silencing; however, integration of publically available gene expression data indicates that 75% of the frequently hypermethylated genes were most likely already lowly or not expressed in normal tissue. Collectively, our study provides genome-wide DNA methylation maps of CRC, comprehensive lists of DMRs, and gives insights into the role of aberrant DNA methylation in CRC formation. |
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Keywords: | DNA methylation colorectal cancer biomarkers H3K27me3 gene expression Illumina sequencing |
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