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Identification and Characterization of MYC Regulatory Elements: Links to Prostate Cancer

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Final summary rept. 15 May 2010-30 Aug 2012

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Prostate cancer is the most common cancer diagnosed in males in the developed world. Genome-wide association studies GWAS have greatly helped in the identification of common risk variants associated with complex diseases such as cancer routinely, these associated polymorphisms are located within gene deserts and other type of non-coding DNA. A striking example of GWAS implicating non-coding variants in the etiology of cancer can be seen on chromosome 8q24, where numerous studies have reported associations between prostate and other cancer and variants concentrated within a 1.2Mb gene desert. Although there are no genes within the interval, the proto-oncogene MYC lies just downstream of the gene desert, raising the possibility that the associated risk regions may harbor long-range cis-regulatory elements such as enhancers involved in the tissue-specific transcriptional regulation of MYC. To date, we have located and characterized an in vivo prostate enhancer encompassing the prostate cancer associated SNPrs6983267. Furthermore, we demonstrated that this enhancer exhibits allele-specific activity in developing and mature mouse prostates, mimicking MYC expression. Our findings help advance the field s understanding of the mechanistic reason for the overwhelming association seen between this 8q24 gene desert and prostate cancer.

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  • Medicine and Medical Research

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