Lessons from Functional Analysis of Genome-Wide Association Studies
Cet article passe en revue les travaux récents sur les mécanismes d'action des polymorphismes à simple nucléotide, pour la plupart localisés en dehors de régions codantes, identifiés dans des études d'association sur le génome entier
Most cancer-associated single-nucleotide polymorphisms (SNP) identified using genome-wide association studies are located outside of protein-coding regions, and their significance and mode of action have been a source of continuing debate. One proposed mechanism of action of the SNPs is that they would affect the activity of enhancer elements regulating critical target genes. In this review, we summarize recent results that substantiate this model. These studies have identified a cancer-specific enhancer element at the 8q24 gene desert that controls the expression of the MYC oncogene. We further discuss implications of the observed difference between normal growth control and cancer for drug development, and the inherent features of genome-wide association studies that may specifically lead to identification of disease-specific regulatory elements. Cancer Res; 73(14); 1–5. ©2013 AACR.
Cancer Research , article en libre accès, 2013