Lessons from functional analysis of genome-wide association studies
Inderpreet Sur1, Sari Tuupanen, Thomas Whitington
1Department of Biosciences and Nutrition, SciLife Center, Karolinska Institutet, Clinical Research Center, Karolinska University Hospital, Stockholm, Sweden.
Cancer Research
|July 9, 2013
Summary
Most cancer-associated single-nucleotide polymorphisms (SNPs) influence gene expression by affecting enhancer activity. A cancer-specific enhancer in the 8q24 gene desert regulates the MYC oncogene, offering insights for drug development.
Area of Science:
- Genomics
- Cancer Biology
- Epigenetics
Background:
- Genome-wide association studies (GWAS) frequently identify cancer-associated single-nucleotide polymorphisms (SNPs) in non-coding regions.
- The functional significance and mechanisms of action for these non-coding SNPs remain under investigation.
- A leading hypothesis suggests these SNPs may alter enhancer activity, thereby modulating the expression of critical genes.
Purpose of the Study:
- To review recent evidence supporting the role of SNPs in modulating enhancer activity in cancer.
- To highlight the identification and function of a specific cancer-associated enhancer.
- To discuss the implications for cancer drug development and GWAS findings.
Main Methods:
- Literature review of studies investigating non-coding SNPs and gene regulation.
- Analysis of research identifying functional enhancer elements associated with cancer.
- Examination of the MYC oncogene and its regulatory elements.
Main Results:
- Recent studies provide substantial evidence that SNPs can affect enhancer function.
- A specific cancer-associated enhancer element located in the 8q24 gene desert has been identified.
- This enhancer is shown to control the expression of the MYC oncogene, a key player in cancer.
Conclusions:
- Non-coding SNPs, particularly those affecting enhancers, represent a significant mechanism in cancer development.
- The identified 8q24 enhancer provides a model for understanding how genetic variations drive oncogene expression in cancer.
- Understanding these disease-specific regulatory elements has potential implications for targeted cancer therapies and refining GWAS interpretations.
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