Researchers identify genomic regions in DNA with hypermethylation, abundant MSRE sites, and low methylation levels that can be amplified and detected using MSRE-PCR analysis in diverse types of tumor DNA and normal tissue.
A pair of U.S. researchers from Johns Hopkins University in Baltimore, Maryland, and from Genmab—an international biotech company in Princeton, New Jersey—collaborated in a study to demonstrate: “Selective amplification of hypermethylated DNA from diverse tumor types via MSRE-PCR.” This study was published as the cover paper of journal Volume 11, Issue #47 in Oncotarget.
Methylation Errors
Methylation is an important process in multiple functions in human DNA, including gene regulation and silencing through the recruitment of proteins. After every cellular DNA replication cycle, DNA methyltransferase (DNMT) enzymes aid in performing on-the-spot DNA methylation to lock genes in the “off” position. DNMT enzymes help to preserve DNA methylation, however, as a frequently occurring process, inaccuracies are known to occur.
Errors in DNA methylation can include hypermethylation, which can lead to improper gene silencing in, for instance, tumor suppressor genes in cancer cells. Researchers in this study note that DNA methylation biomarkers are increasingly utilized for the detection, prognosis, and monitoring of cancer.
“Global epigenetic changes, including DNA methylation, are widely regarded as a hallmark of cancer [1]. Alterations include a decrease in overall CpG methylation levels coupled with discrete regions of hypermethylation, typically localized in the promoter-associated CpG islands.”
CpG Islands
CpG islands (CGIs) are detectable genomic patterns of promoter regions usually found at the start of genes. CGIs have been considered to be one of the best predictors researchers can use to define active, or potentially active, genes. In cancer and many other disease processes, gene promoter CGIs can become hypermethylated in error—switching off important tumor suppressor and growth regulating genes—which can be replicated through cell division and contribute to disease progression.
“Here we use publicly-available whole genome bisulfite sequencing data to identify differentially methylated regions (cDMRs) in diverse tumor types and further define a set of genomic target regions that have optimal characteristics for Methylation Sensitive Restriction Enzyme-PCR (MSRE-PCR)-based detection: conserved hypermethylation in tumors, abundant MSRE sites and low methylation levels in normal tissues.”
Hypermethylated DNA from Diverse Tumor Types
The researchers in this study sought to specifically, selectively, and non-invasively amplify and identify tumor DNA without causing damage to surrounding tissue. They used multiplexed Methylation Sensitive Restriction Enzyme-PCR (MSRE-PCR) assays and publicly available datasets from diverse tumors and normal tissue in the lung, breast, stomach, colon, and blood.
They found that CGIs and genomic regions with hypermethylation, abundant MSRE sites, and low methylation levels in normal tissue provide target regions to detect diverse tumor types of DNA using MSRE-PCR. Researchers in this paper also advise the testing of more samples using MSRE-PCR in future studies.
“The selective amplification of tumor-derived DNA via MSRE-PCR may have utility in the development of non-invasive cancer detection and surveillance strategies.”
Click here to read the full scientific paper, published in Oncotarget.
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