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Sensitive digital quantification of DNA methylation in clinical samples.

Publication ,  Journal Article
Li, M; Chen, W-D; Papadopoulos, N; Goodman, SN; Bjerregaard, NC; Laurberg, S; Levin, B; Juhl, H; Arber, N; Moinova, H; Durkee, K; Schmidt, K ...
Published in: Nat Biotechnol
September 2009

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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Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

September 2009

Volume

27

Issue

9

Start / End Page

858 / 863

Location

United States

Related Subject Headings

  • Vimentin
  • Sensitivity and Specificity
  • Humans
  • Genetic Techniques
  • Feces
  • DNA, Neoplasm
  • DNA Methylation
  • Colorectal Neoplasms
  • Biomarkers, Tumor
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, M., Chen, W.-D., Papadopoulos, N., Goodman, S. N., Bjerregaard, N. C., Laurberg, S., … Vogelstein, B. (2009). Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol, 27(9), 858–863. https://doi.org/10.1038/nbt.1559
Li, Meng, Wei-Dong Chen, Nickolas Papadopoulos, Steven N. Goodman, Niels Christian Bjerregaard, Søren Laurberg, Bernard Levin, et al. “Sensitive digital quantification of DNA methylation in clinical samples.Nat Biotechnol 27, no. 9 (September 2009): 858–63. https://doi.org/10.1038/nbt.1559.
Li M, Chen W-D, Papadopoulos N, Goodman SN, Bjerregaard NC, Laurberg S, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009 Sep;27(9):858–63.
Li, Meng, et al. “Sensitive digital quantification of DNA methylation in clinical samples.Nat Biotechnol, vol. 27, no. 9, Sept. 2009, pp. 858–63. Pubmed, doi:10.1038/nbt.1559.
Li M, Chen W-D, Papadopoulos N, Goodman SN, Bjerregaard NC, Laurberg S, Levin B, Juhl H, Arber N, Moinova H, Durkee K, Schmidt K, He Y, Diehl F, Velculescu VE, Zhou S, Diaz LA, Kinzler KW, Markowitz SD, Vogelstein B. Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol. 2009 Sep;27(9):858–863.

Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

September 2009

Volume

27

Issue

9

Start / End Page

858 / 863

Location

United States

Related Subject Headings

  • Vimentin
  • Sensitivity and Specificity
  • Humans
  • Genetic Techniques
  • Feces
  • DNA, Neoplasm
  • DNA Methylation
  • Colorectal Neoplasms
  • Biomarkers, Tumor