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Updated: Jun 17, 2026
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human
H H Cheung1, T L Lee, A J Davis
1Laboratory of Clinical Genomics, Section on Developmental Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Background:
Testicular germ cell tumour (TGCT) is the most common malignant tumour in young males. Although aberrant DNA methylation is implicated in the pathophysiology of many cancers, only a limited number of genes are known to be epigenetically changed in TGCT. This report documents the genome-wide analysis of differential methylation in an in vitro model culture system. Interesting genes were validated in TGCT patient samples.
Methods:
In this study, we used methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to identify differentially methylated regions (DMRs).
Results:
We identified 35 208 DMRs. However, only a small number of DMRs mapped to promoters. A genome-wide analysis of gene expression revealed a group of differentially expressed genes that were regulated by DNA methylation. We identified several candidate genes, including APOLD1, PCDH10 and RGAG1, which were dysregulated in TGCT patient samples. Surprisingly, APOLD1 had previously been mapped to the TGCT susceptibility locus at 12p13.1, suggesting that it may be important in TGCT pathogenesis. We also observed aberrant methylation in the loci of some non-coding RNAs (ncRNAs). One of the ncRNAs, hsa-mir-199a, was downregulated in TGCT patient samples, and also in our in vitro model culture system.
Conclusion:
This report is the first application of MeDIP-chip for identifying epigenetically regulated genes and ncRNAs in TGCT. We also demonstrated the function of intergenic and intronic DMRs in the regulation of ncRNAs.
Insights
This study identified widespread DNA methylation changes in testicular germ cell tumors (TGCT) using MeDIP-chip. Aberrantly methylated genes and non-coding RNAs, like hsa-mir-199a, were found in TGCT patients and models.
Area of Science:
- Oncology
- Epigenetics
- Genomics
Background:
- Testicular germ cell tumour (TGCT) is the most common male cancer in young adults.
- Aberrant DNA methylation is implicated in cancer, but few genes are known to be epigenetically altered in TGCT.
- This study performed a genome-wide analysis of differential methylation in an in vitro TGCT model.
Purpose of the Study:
- To identify novel epigenetically regulated genes and non-coding RNAs (ncRNAs) in TGCT.
- To investigate the role of DNA methylation in TGCT pathogenesis.
- To validate findings in patient samples.
Main Methods:
- Methylated DNA immunoprecipitation (MeDIP) coupled with whole-genome tiling arrays (MeDIP-chip) was employed.
- Genome-wide gene expression analysis was conducted.
- Candidate genes and ncRNAs were validated in TGCT patient samples.
Main Results:
- 35,208 differentially methylated regions (DMRs) were identified, with few mapping to promoters.
- DNA methylation regulated a subset of differentially expressed genes, including APOLD1, PCDH10, and RGAG1, which were dysregulated in TGCT.
- Aberrant methylation was observed in ncRNA loci, with hsa-mir-199a found to be downregulated in TGCT patients and the in vitro model.
Conclusions:
- This is the first study to apply MeDIP-chip for identifying epigenetically regulated genes and ncRNAs in TGCT.
- The study demonstrated the role of intergenic and intronic DMRs in regulating ncRNAs.
- APOLD1, located at a known TGCT susceptibility locus, emerged as a potential key player in TGCT pathogenesis.
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