Identification of DNA methylation changes associated with human gastric cancer

Jung Hoon Park, Jinah Park, Jung Kyoon Choi, Jaemyun Lyu, Min Gyun Bae, Young Gun Lee, Jae Bum Bae, Dong Yoon Park, Han Kwang Yang, Tae You Kim, Young Joon Kim

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Article number82
JournalBMC Medical Genomics
Volume4
DOIs
Publication statusPublished - 2011 Dec 5

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CpG Islands
DNA Methylation
Stomach Neoplasms
Epigenomics
Methylation
Genes
Genetic Epigenesis
Molecular Sequence Annotation
Histones
Exons
Neoplasms
Down-Regulation
Lymph Nodes
Genome
Gene Expression
DNA

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics

Cite this

Park, Jung Hoon ; Park, Jinah ; Choi, Jung Kyoon ; Lyu, Jaemyun ; Bae, Min Gyun ; Lee, Young Gun ; Bae, Jae Bum ; Park, Dong Yoon ; Yang, Han Kwang ; Kim, Tae You ; Kim, Young Joon. / Identification of DNA methylation changes associated with human gastric cancer. In: BMC Medical Genomics. 2011 ; Vol. 4.
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Park, JH, Park, J, Choi, JK, Lyu, J, Bae, MG, Lee, YG, Bae, JB, Park, DY, Yang, HK, Kim, TY & Kim, YJ 2011, 'Identification of DNA methylation changes associated with human gastric cancer', BMC Medical Genomics, vol. 4, 82. https://doi.org/10.1186/1755-8794-4-82

Identification of DNA methylation changes associated with human gastric cancer. / Park, Jung Hoon; Park, Jinah; Choi, Jung Kyoon; Lyu, Jaemyun; Bae, Min Gyun; Lee, Young Gun; Bae, Jae Bum; Park, Dong Yoon; Yang, Han Kwang; Kim, Tae You; Kim, Young Joon.

In: BMC Medical Genomics, Vol. 4, 82, 05.12.2011.

Research output: Contribution to journalArticle

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T1 - Identification of DNA methylation changes associated with human gastric cancer

AU - Park, Jung Hoon

AU - Park, Jinah

AU - Choi, Jung Kyoon

AU - Lyu, Jaemyun

AU - Bae, Min Gyun

AU - Lee, Young Gun

AU - Bae, Jae Bum

AU - Park, Dong Yoon

AU - Yang, Han Kwang

AU - Kim, Tae You

AU - Kim, Young Joon

PY - 2011/12/5

Y1 - 2011/12/5

N2 - 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.

AB - 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.

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