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DNA methylation changes in ex-adenoma carcinoma of the large intestine

Cited 18 time in Web of Science Cited 18 time in Scopus
Authors
Kwon, Hyeong-Ju; Kim, Jung Ho; Bae, Jeong Mo; Cho, Nam-Yun; Kang, Gyeong Hoon; Kim, Tae-You
Issue Date
2010-10
Publisher
SPRINGER
Citation
VIRCHOWS ARCHIV; Vol.457 4; 433-441
Keywords
CpG islandEx-adenoma carcinomaHypermethylationDNA methylation changes
Abstract
Ex-adenoma carcinoma (EAC) is a carcinoma with contiguous adenoma element in its vicinity which provides a morphological evidence for adenoma-carcinoma sequence. During multistep colorectal carcinogenesis, promoter CpG island hypermethylation has been known to increase in a stepwise manner whereas diffuse genomic hypomethylation has been known to be an early event and not progress. However, some controversies exist. EAC is a good model to study the timing of hypermethylation and hypomethylation changes during multistep carcinogenesis, which this study aimed to elucidate. We analyzed 39 cases of EAC for their methylation status in eight DNA methylation markers of CpG island methylator phenotype (CIMP) panel, ten CIMP-nonrelated, cancer-specific markers, and three repetitive DNA elements (ALU, LINE-1, and SAT2) using MethyLight assay or combined bisulfite restriction analysis. Twenty-two cases of cancers had contiguous tubulovillous adenomas and 17 cases had contiguous tubular adenomas. Regardless of CIMP markers or nonrelated markers, a significant increase in the number of methylated genes was found from normal mucosa to adenoma, whereas no increase was found from adenoma to carcinoma. Both ALU and LINE-1 showed a significant decrease of methylation levels from normal mucosa to adenoma (p < 0.05), but there is no difference between adenoma and cancer. However, SAT2 methylation level exhibited a stepwise decrease from normal mucosa to adenoma to cancer. Our findings suggest that morphological progression from traditional adenoma to carcinoma does not appear to be accompanied by increases in promoter CpG island hypermethylation or repetitive DNA hypomethylation, except for SAT2 hypomethylation which showed continuous progression during multistep carcinogenesis.
ISSN
0945-6317
Language
English
URI
https://hdl.handle.net/10371/77665
DOI
https://doi.org/10.1007/s00428-010-0958-9
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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