Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition
Autor: | Asaf Hellman, Dvir Aran |
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Rok vydání: | 2013 |
Předmět: |
Regulation of gene expression
Genetics Cancer Methylation DNA Methylation Regulatory Sequences Nucleic Acid Biology medicine.disease General Biochemistry Genetics and Molecular Biology DNA sequencing Enhancer Elements Genetic Neoplasms DNA methylation medicine Animals Humans Genetic Predisposition to Disease Gene RNA-Directed DNA Methylation Epigenomics |
Zdroj: | BioEssays. 36:184-190 |
ISSN: | 0265-9247 |
Popis: | Paradoxically, DNA sequence polymorphisms in cancer risk loci rarely correlate with the expression of cancer genes. Therefore, the molecular mechanism underlying an individual's susceptibility to cancer has remained largely unknown. However, recent evaluations of the correlations between DNA methylation and gene expression levels across healthy and cancerous genomes have revealed enrichment of disease-related DNA methylation variations within disease-associated risk loci. Moreover, it appears that transcriptional enhancers embedded in cancer risk loci often contain DNA methylation sites that closely define the expression of prominent cancer genes, despite the lack of significant correlations between gene expression levels and the surrounding disease-associated polymorphic sequences. We suggest that DNA methylation variations may obscure the effect of co-residing risk sequence alleles. Analysis of enhancer methylation data may help to reveal the regulatory circuits underlying predisposition to cancers and other common diseases. |
Databáze: | OpenAIRE |
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