Editor's ChoiceBiomarkers for Cancer

Monitoring Methylation

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Science Translational Medicine  14 Oct 2009:
Vol. 1, Issue 2, pp. 2ec8
DOI: 10.1126/scitranslmed.3000469

Mammalian DNA is dotted with methyl groups—covalent modifications to the DNA that affect gene expression and are sometimes altered in disease. For example, cancer cells display aberrant methylation patterns. In general, methylation is reduced in cancer cell genomes, but in certain regions, methylation is enhanced, and this hypermethylation is linked to gene silencing. Because cancer-associated hypermethylation tends to affect the identical residues in a given gene's regulatory region, whereas cancer-associated DNA mutations can occur in multiple places in a particular gene, methylation patterns have advantages over DNA as biomarkers. Diagnosis of cancer from plasma, urine, or fecal samples requires detection of cancer-associated DNA that is only a small percentage of the total DNA. Current methods for methylation detection involve chemical conversion of methylated DNA residues followed by PCR or hybridization. The signal-to-noise ratio could be greatly improved if methylated and unmethylated fragments could be counted one-by-one. Li et al. now describe such a digital approach, called methyl-BEAMing, which provides absolute quantification of the number of methylated fragments in a sample. In this technique, individual DNA molecules are chemically treated, amplified in nanocompartments, and then analyzed, allowing detection of one methylated molecule in 5000 unmethylated molecules in clinical samples. In one example, using methyl-BEAMing of plasma samples, the investigators detected 59% of colorectal cancers. For early stage cancers, this assay was much more sensitive than a different serum-based assay. The ability to detect very rare methylation events should be applicable to a range of diagnostic and prognostic situations.

M. Li et al., Sensitive digital quantification of DNA methylation in clinical samples. Nat. Biotechnol.27, 858–863 (2009). http://www.nature.com/nbt/journal/v27/n9/abs/nbt.1559.html

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