Dataset Information

Detailed methylation map of LINE-1 5'-promoter region reveals hypomethylated CpG hotspots associated with tumor tissue specificity.

ABSTRACT:

Background

Long interspersed nuclear elements (LINE-1) sequences constitute a substantial portion of the human genome, and their methylation often correlating with global genomic methylation. Previous studies have highlighted the feasibility of using LINE-1 methylation to discriminate tumors from healthy tissues. However, most studies are based on only a few specific LINE-1 CpG sites.

Methods

Herein, we have performed a systematic fine-scale analysis of methylation at 14 CpGs located in the 5'-region of consensus LINE-1, in bladder, colon, prostate, and gastric tumor tissues using a global degenerate approach.

Results

Our results reveal variable methylation levels between different CpGs, as well as some tissue-specific differences. Trends toward hypomethylation were observed in all tumors types to certain degrees, showing statistically significance in bladder and prostate tumors. Our data points toward the presence of unique LINE-1 DNA methylation patterns for each tumor type and tissue, indicating that not the same CpGs will be informative for testing in all tumor types.

Conclusion

This study provides an accurate guide that will help to design further assays that could avoid artifacts and explain the variability of obtained LINE-1 methylation values between different studies.

SUBMITTER: Sharma A

PROVIDER: S-EPMC6503062 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Detailed methylation map of LINE-1 5'-promoter region reveals hypomethylated CpG hotspots associated with tumor tissue specificity.

Sharma Amit A Jamil Muhammad A MA Nuesgen Nicole N Dauksa Albertas A Gulbinas Antanas A Schulz Wolfgang A WA Oldenburg Johannes J El-Maarri Osman O

Molecular genetics & genomic medicine 20190406 5

<h4>Background</h4>Long interspersed nuclear elements (LINE-1) sequences constitute a substantial portion of the human genome, and their methylation often correlating with global genomic methylation. Previous studies have highlighted the feasibility of using LINE-1 methylation to discriminate tumors from healthy tissues. However, most studies are based on only a few specific LINE-1 CpG sites.<h4>Methods</h4>Herein, we have performed a systematic fine-scale analysis of methylation at 14 CpGs loca ...[more]

PMID: 30955237

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Project description:BackgroundRecently, much attention has been focused on gaining a better understanding of the different populations of cells within a tumor and their contribution to cancer progression. One of the most commonly used methods to isolate a more aggressive sub-population of cells utilizes cell sorting based on expression of certain cell adhesion molecules. A recently established method we developed is to isolate these more aggressive cells based on their properties of increased invasive ability. These more invasive cells have been previously characterized as tumor initiating cells (TICs) that have a stem-like genomic signature and express a number of stem cell genes including Oct3/4 and Nanog and are more tumorigenic compared to their 'non-invasive' counterpart. They also have a profile reminiscent of cells undergoing a classic pattern of epithelial to mesenchymal transition or EMT. Using this model of invasion, we sought to investigate which genes are under epigenetic control in this rare population of cells. Epigenetic modifications, specifically DNA methylation, are key events regulating the process of normal human development. To determine the specific methylation pattern in these invasive prostate cells, and if any developmental genes were being differentially regulated, we analyzed differences in global CpG promoter methylation.ResultsDifferentially methylated genes were determined and select genes were chosen for additional analyses. The non-receptor tyrosine kinase BMX and transcription factor SOX1 were found to play a significant role in invasion. Ingenuity pathway analysis revealed the methylated gene list frequently displayed genes from the IL-6/STAT3 pathway. Cells which have decreased levels of the targets BMX and SOX1 also display loss of STAT3 activity. Finally, using Oncomine, it was determined that more aggressive metastatic prostate cancers in humans also have higher levels of both Stat3 and Sox1.ConclusionsUsing this method we can begin to understand which genes are epigenetically regulated in the invasive population compared to the bulk tumor cells. These aggressive sub-populations of cells may be linked to the cancer stem cell hypothesis, making their patterns of epigenetic regulation very attractive for biomarker analysis.

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Dataset Information

Detailed methylation map of LINE-1 5'-promoter region reveals hypomethylated CpG hotspots associated with tumor tissue specificity.

Background

Methods

Results

Conclusion

Publications

Detailed methylation map of LINE-1 5'-promoter region reveals hypomethylated CpG hotspots associated with tumor tissue specificity.

Similar Datasets

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