Document Detail

DNA methylation changes in ex-adenoma carcinoma of the large intestine.
MedLine Citation:
PMID:  20711609     Owner:  NLM     Status:  MEDLINE    
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.
Hyeong-Ju Kwon; Jung Ho Kim; Jeong Mo Bae; Nam-Yun Cho; Tae-You Kim; Gyeong Hoon Kang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-14
Journal Detail:
Title:  Virchows Archiv : an international journal of pathology     Volume:  457     ISSN:  1432-2307     ISO Abbreviation:  Virchows Arch.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423843     Medline TA:  Virchows Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  433-41     Citation Subset:  IM    
Department of Pathology, Seoul National University College of Medicine, Chongno-gu, Seoul 110-744, South Korea.
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MeSH Terms
Adenoma / genetics*
Carcinoma / genetics*
Colorectal Neoplasms / genetics*
CpG Islands*
DNA Methylation*
Repetitive Sequences, Nucleic Acid

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