title: Identification of radiation-induced aberrant hypomethylation in colon cancer.
abstract: BACKGROUND
  Exposure to ionizing radiation (IR) results in the simultaneous activation or downregulation of multiple signaling pathways that play critical roles in cell type-specific control of survival or death. IR is a well-known genotoxic agent and human carcinogen that induces cellular damage through direct and indirect mechanisms. However, its impact on epigenetic mechanisms has not been elucidated, and more specifically, little information is available regarding genome-wide DNA methylation changes in cancer cells after IR exposure. Recently, genome-wide DNA methylation profiling technology using the Illumina HumanMethylation450K platform has emerged that allows us to query >450,000 loci within the genome. This improved technology is capable of identifying genome-wide DNA methylation changes in CpG islands and other CpG island-associated regions.
  
  
  RESULTS
  In this study, we employed this technology to test the hypothesis that exposure to IR not only induces differential DNA methylation patterns at a genome-wide level, but also results in locus- and gene-specific DNA methylation changes. We screened for differential DNA methylation changes in colorectal cancer cells after IR exposure with 2 and 5 Gy. Twenty-nine genes showed radiation-induced hypomethylation in colon cancer cells, and of those, seven genes showed a corresponding increase in gene expression by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, we performed chromatin immunoprecipitation (ChIP) to confirm that the DNA-methyltransferase 1 (DNMT1) level associated with the promoter regions of these genes correlated with their methylation level and gene expression changes. Finally, we used a gene ontology (GO) database to show that a handful of hypomethylated genes induced by IR are associated with a variety of biological pathways related to cancer.
  
  
  CONCLUSIONS
  We identified alterations in global DNA methylation patterns and hypomethylation at specific cancer-related genes following IR exposure, which suggests that radiation exposure plays a critical role in conferring epigenetic alterations in cancer.
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, South Korea. 82jinhan@pusan.ac.kr.
authors.forename: Jin-Han
authors.initials: JH
authors.lastname: Bae
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, South Korea. jgkim210@gmail.com.
authors.forename: Joong-Gook
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, South Korea. khjhk33@gmail.com.
authors.forename: Kyu
authors.initials: K
authors.lastname: Heo
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, South Korea. kmyang@dirams.re.kr.|Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, 139-709, Korea. kmyang@dirams.re.kr.
authors.forename: Kwangmo
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Inje University Haeundae Paik hospital, Busan, 612-896, South Korea. kto0440@paik.ac.kr.
authors.forename: Tae-Oh
authors.initials: TO
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 619-953, South Korea. jmyi@diram.re.kr.
authors.forename: Joo Mi
authors.initials: JM
authors.lastname: Yi
mesh_terms: D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics* / Q000528:radiation effects; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D015894:Genome, Human / Q000528:radiation effects; D045325:HCT116 Cells; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011839:Radiation, Ionizing
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases