|Figure 7: The 8q24 gene desert enhancers.(A) Cartoon of distal c-MYC enhancers, including positions
where SNPs that are associated with the specific cancer types have been identified.
Consistent with the disease-specific association of the various SNP regions, each
enhancer makes contact with the MYC promoter in a tissue-type specific manner. The
breast and prostate 2 enhancers are shown for illustration. (B). The prostate/colon-specific
enhancer 3 makes loop-mediated contacts with the c-MYC promoter in prostate/colon
cells, poising the promoter for activation. Subsequent activation of MYC transcription
can be achieved by activation of the Wnt/APC/β-catenin pathway (APC), which causes
β-catenin/TCF/LEF1 to occupy a remaining site on the enhancer (orange circle), stimulating
MYC expression. Alternatively (or more likely additionally in colorectal carcinomas)
β-catenin/TCF/LEF1 can be directly stimulated by mutations such as the minor SNP allele
of rs6983267, which creates a consensus binding site for β-catenin/TCF/LEF1.