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Open Access Highly Accessed Research article

Identification of DNA methylation changes associated with human gastric cancer

Jung-Hoon Park1, Jinah Park3, Jung Kyoon Choi45, Jaemyun Lyu1, Min-Gyun Bae1, Young-Gun Lee1, Jae-Bum Bae1, Dong Yoon Park1, Han-Kwang Yang3, Tae-You Kim3* and Young-Joon Kim12*

Author Affiliations

1 Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, Korea

2 Department of Integrated Omics for Biomedical Science, WCU Program of Graduate School, Yonsei University, Seoul, Korea

3 Cancer Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

4 Department of Bio and Brain Engineering, KAIST, Daejeon, Korea

5 Computational and Systems Biology, Genome Institute of Singapore, Singapore, Singapore

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BMC Medical Genomics 2011, 4:82  doi:10.1186/1755-8794-4-82

Published: 2 December 2011

Abstract

Background

Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult.

Methods

We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay) in combination with a genome analyzer and a new normalization algorithm.

Results

We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the HOX and histone gene families. We also discovered long-range epigenetic silencing (LRES) regions in gastric cancer tissue and identified several hypermethylated genes (MDM2, DYRK2, and LYZ) within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue.

Conclusions

Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.