Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues.
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.
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
Femke
F
Simmer
Arie B
AB
Brinkman
Yassen
Y
Assenov
Filomena
F
Matarese
Anita
A
Kaan
Lina
L
Sabatino
Alberto
A
Villanueva
Dori
D
Huertas
Manel
M
Esteller
Thomas
T
Lengauer
Christoph
C
Bock
Vittorio
V
Colantuoni
Lucia
L
Altucci
Hendrik G
HG
Stunnenberg
D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003106:Colon / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000502:physiology; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012016:Reference Values
D014408:Biomarkers, Tumor; D006657:Histones