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

Hyeong Ju Kwon, Jung Ho Kim, Jeong Mo Bae, Nam Yun Cho, Tae You Kim, Gyeong Hoon Kang

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19 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)433-441
Number of pages9
JournalVirchows Archiv
Issue number4
Publication statusPublished - 2010 Oct

Bibliographical note

Funding Information:
Acknowledgments This study is supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A091081), a grant from the Seoul National University Hospital Research Fund (30-2009-001-0), and a Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093820).

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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