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- Title
Sensitive digital quantification of DNA methylation in clinical samples.
- Authors
Meng Li; Wei-dong Chen; Papadopoulos, Nickolas; Goodman, Steven N.; Bjerregaard, Niels Christian; Laurberg, Søren; Levin, Bernard; Juhl, Hartmut; Arber, Nadir; Moinova, Helen; Durkee, Kris; Schmidt, Kerstin; Yiping He; Diehl, Frank; Velculescu, Victor E.; Zhou, Shibin; Diaz Jr., Luis A.; Kinzler, Kenneth W.; Markowitz, Sanford D.; Vogelstein, Bert
- Abstract
Analysis of abnormally methylated genes is increasingly important in basic research and in the development of cancer biomarkers. We 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. We demonstrate enumeration of as few as one methylated molecule in ∼5,000 unmethylated molecules in DNA from plasma or fecal samples. 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. 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.
- Subjects
METHYLATION; BIOMARKERS; DNA; COLON cancer; ANTIGENS; FECES
- Publication
Nature Biotechnology, 2009, Vol 27, Issue 9, p858
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt.1559