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Abstract:
Most cancer somatic alterations occur in the noncoding portion of the human genome, which contains important cis-regulatory regions acting as genetic switches to ensure gene expression occurs at correct times and intensities in correct tissues. However, the identification of critical noncoding cancer driver events has been mostly limited to a few examples with high recurrence or high functional impact. Transcription factors (TFs) are key proteins binding to cis-regulatory regions at their TF binding sites to modulate the rate of gene transcription. As cancer is a disease of disrupted cellular regulation, it is critical to analyze these regions to highlight patient somatic mutations and epigenetic modifications altering the gene regulatory program of the cells. In this talk, I will present our recent works on the interplay between TF binding, somatic mutations, and DNA methylation alteration that shifts the gene regulatory program in patients cancer cells.