Monday, August 8, 2011

Quantitating DNA methylation: traps for the unwary!

DNA methylation is rapidly becoming a useful biomarker  for diagnosis and prognosis of disease, as well as for predicting patient response to treatment.  However the gold standard for analyzing DNA methylation base-by-base, bisulfite sequencing, is time consuming and therefore not conducive for use in a molecular pathology lab.  Most labs get around this by using quantitative methylation-specific PCR, COBRA or pyrosequencing - however these techniques provide an average estimation of methylation levels at particular sites.  This would be OK if each allele were identically methylated; however as Thomas Mikesa, Ida Candiloro and Alex Dobrovic detail in a recent review, DNA methylation is frequently heterogeneous, and comprised of multiple "epialleles" - each with its' own specific methylation pattern.  In the review, Mikesa et al. critically assess the current techniques used to quantitate methylation in the context of epialleles, and provide a  novel methodology that could serve to solve this problem.  You can read the review for yourself, and best of all it is free!  Get it at the link below:

The implications of heterogeneous DNA methylation for the accurate quantification of methylation, by Mikesa et al.

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