Efficient and Sensitive Bisulfite-Free Methylation Detection Approach for Low-Abundance and Highly Fragmented cfDNA.

Journal: Analytical chemistry

This study presents the development of a novel, highly sensitive methylation detection method for fragmented circulating cell-free DNA (cfDNA) called dRE-STEM. This method combines double restriction enzyme digestion with specific terminal-mediated PCR.

Unlike traditional methods, dRE-STEM does not require bisulfite conversion, which simplifies the process.

It was validated in a colorectal cancer case-control study, with the following results:

  • Detection of methylation ratios as low as 3% from only 4 ng of cfDNA
  • Diagnostic sensitivity of 80.2%
  • Diagnostic specificity of 80.9%
  • Performance superior to conventional protein biomarkers

The dRE-STEM method shows promise for accurate methylation quantification in low-abundance, fragmented cfDNA, supporting its potential use in routine clinical cancer diagnostics.

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