Sensitive digital quantification of DNA methylation in clinical samples
Open accessAbstract
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 approximately 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.
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Some transcription factors that lack a methyl-CpG binding domain can interact with methylated DNA.
“evidence is emerging to suggest that transcription factors lacking a MBD can also interact with methylated DNA”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [23]
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References 31 · Cited by 341
Research works printed but not linked: 1
- [15]Vogelstein B Kinzler KW Digital PCR Proc Natl Acad Sci U S A 96 9236 9241 1999 10430926 PMC17763
- Authors
- Li, M., Chen, W.-D., Papadopoulos, N., Goodman, S. N., Bjerregaard, N. C., Laurberg, S., Levin, B., Juhl, H., Arber, N., Moinova, H., Durkee, K., Schmidt, K., He, Y., Diehl, F., Velculescu, V. E., Zhou, S., Diaz, L. A., Kinzler, K. W., Markowitz, S. D., & Vogelstein, B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Aarhus University (DK)
- The University of Texas MD Anderson Cancer Center (US)
- Israelitisches Krankenhaus (DE)
- Tel Aviv University (IL)
- Exact Sciences (United States) (US)
- Corresponding author
- Markowitz, Sanford D
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2009-08-16
- Volume
- 27
- Issue
- 9
- Pages
- 858-863
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC2847606
- OpenAlex
- W2139144040
- Cited by
- 341
- References
- 31
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 11 · 2023: 17 · 2022: 16 · 2021: 21 · 2020: 12 · 2019: 16 · 2018: 21 · 2017: 28 · 2016: 28 · 2015: 32 · 2014: 20 · 2013: 21 · 2012: 32
- FWCI
- 12.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA43460, R37CA043460, CA120237, P50CA062924, R01CA120237, CA 62924)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Keywords
- DNA methylation, digital quantification, epigenetic biomarkers, tumor markers, colorectal cancer, plasma DNA, fecal DNA, early cancer detection, advanced adenoma, carcinoembryonic antigen, single-molecule detection
- MeSH terms
- DNA, Neoplasm, Feces, Genetic Techniques, Humans, Sensitivity and Specificity, Biomarkers, Tumor, Vimentin, Colorectal Neoplasms, DNA Methylation
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