Chemically induced DNA hypomethylation in breast carcinoma cells detected by the amplification of intermethylated sites

Breast Cancer Research : BCR
Bekim SadikovicDavid I Rodenhiser

Abstract

Compromised patterns of gene expression result in genomic instability, altered patterns of gene expression and tumour formation. Specifically, aberrant DNA hypermethylation in gene promoter regions leads to gene silencing, whereas global hypomethylation events can result in chromosomal instability and oncogene activation. Potential links exist between environmental agents and DNA methylation, but the destabilizing effects of environmental exposures on the DNA methylation machinery are not understood within the context of breast cancer aetiology. We assessed genome-wide changes in methylation patterns using a unique methylation profiling technique called amplification of intermethylated sites (AIMS). This method generates easily readable fingerprints that represent the investigated cell line's methylation profile, based on the differential cleavage of DNA with methylation-specific isoschisomeric restriction endonucleases. We validated this approach by demonstrating both unique and reoccurring sites of genomic hypomethylation in four breast carcinoma cell lines treated with the cytosine analogue 5-azacytidine. Comparison of treated with control samples revealed individual bands that exhibited methylation changes, and these bands ...Continue Reading

References

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Citations

May 24, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xiefan FangKristine L Willett
Oct 2, 2007·Toxicology and Applied Pharmacology·Bekim SadikovicDavid I Rodenhiser
Feb 17, 2010·Analytical Biochemistry·Johannes F WentzelPieter J Pretorius
Jan 16, 2017·Molecular and Cellular Endocrinology·Marianne S AndresenGrethe Skretting
Mar 21, 2007·Journal of Cellular Biochemistry·Barbara Gawronska-KozakVeronica Prpic
Mar 23, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dongxu GaoZhenghong Zuo
Dec 3, 2004·Human Molecular Genetics·Jordi FrigolaMiguel A Peinado
Nov 28, 2012·Clinical Chemistry and Laboratory Medicine : CCLM·Andrea Fuso
Dec 11, 2007·The Journal of Biological Chemistry·Bekim SadikovicDavid I Rodenhiser

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Methods Mentioned

BETA
methylation profiling
PCR
X-ray
restriction digests
chemical treatment

Software Mentioned

AIMS
BLAST
Human Genome Browser

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