JHU researchers have developed a technology called BEAMing (Beads, Emulsion, Amplification and Magnetics), which can assess millions of molecules simultaneously for the study of human genetic variation. BEAMing technology converts single DNA molecules into single magnetic beads, each bead possessing thousands of copies of the original DNA molecule. The proportion of one kind of DNA molecule in a population of DNA molecules can be assessed by fluorescent staining and counting via flow cytometry. Flow sorting allows the separation of specific variants that can be verified for further experimentation.
Analysis of abnormally methylated genes is increasingly important in basic research and in the development of cancer biomarkers. JHU scientists have developed methyl-BEAMing technology to enable absolute quantification of the number of methylated molecules in a sample. Individual DNA fragments are amplified and analyzed either by flow cytometry or next-generation sequencing. Enumeration of as few as one methylated molecule in ~5,000 unmethylated molecules in DNA from plasma or fecal samples is demonstrated. Using methylated vimentin as a biomarker in plasma samples, methyl-BEAMing detected 59% of cancer cases. In early-stage colorectal cancers, this sensitivity was four times more than that obtained by assaying serum-carcinoembryonic antigen (CEA). With stool samples, methyl-BEAMing detected 41% of cancers and 45% of advanced adenomas.
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Methyl-BEAMing could be used as a diagnostics tool for screening for known disease mutations, for common and rare epigenetic changes in diseased tissues, and for monitoring of tumor progression in patients undergoing surgery, chemotherapy, and general disease progression. In addition to diagnostic and prognostic applications, this digital quantification of rare methylation events should be applicable to preclinical assessment of new epigenetic biomarkers and quantitative analyses in epigenetic research.
Publications/Associated Cases:
Li, M., Chen, W. -., Papadopoulos, N., Goodman, S. N., Bjerregaard, N. C., Laurberg, S., et al. (2009). Sensitive digital quantification of DNA methylation in clinical samples. Nature Biotechnology, 27(9), 858-863.
