Methylation profiling of normal individuals reveals mosaic promoter methylation of cancer-associated genes.

Oncotarget
Lasse S KristensenAlexander Dobrovic

Abstract

Epigenetic silencing by promoter methylation of genes associated with cancer initiation and progression is a hallmark of tumour cells. As a consequence, testing for DNA methylation biomarkers in plasma or other body fluids shows great promise for detection of malignancies at early stages and/or for monitoring response to treatment. However, DNA from normal leukocytes may contribute to the DNA in plasma and will affect biomarker specificity if there is any methylation in the leukocytes. DNA from 48 samples of normal peripheral blood mononuclear cells was evaluated for the presence of methylation of a panel of DNA methylation biomarkers that have been implicated in cancer. SMART-MSP, a methylation specific PCR (MSP) methodology based on real time PCR amplification, high-resolution melting and strategic primer design, enabled quantitative detection of low levels of methylated DNA. Methylation was observed in all tested mononuclear cell DNA samples for the CDH1 and HIC1 promoters and in majority of DNA samples for the TWIST1 and DAPK1 promoters. APC and RARB promoter methylation, at a lower average level, was also detected in a substantial proportion of DNA samples. We found no BRCA1, CDKN2A, GSTP1 and RASSF1A promoter methylation ...Continue Reading

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Citations

Apr 19, 2013·Current Protocols in Human Genetics·Lasse Sommer KristensenKirsten Grønbæk
Feb 18, 2016·Journal of Neuropathology and Experimental Neurology·Lasse S KristensenHelle Broholm
Dec 19, 2017·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Ji Yun LeeDong Sun Kim
Jan 15, 2015·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Soo Yeun ParkDuk-Hee Lee
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Apr 19, 2018·Nature Reviews. Clinical Oncology·Alexander KochManon van Engeland
Oct 11, 2013·BioTechniques·Hernán G HernándezDiego A Forero

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Methods Mentioned

BETA
electrophoresis
PCR

Software Mentioned

Rotor
MSP
Rotorgene
Gene 6000 Series
SMART
MethyLight

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