Maintenance of gene expression programs is essential to ensure proper functioning of the various cell types that make up the body. To this end, cells have evolved “epigenetic“ regulatory mechanisms, based on the addition of chemical modifications on certain genes. Among these, DNA methylation serves to inactivate certain genes.
In many cancers, the distribution of DNA methylation marks is profoundly altered, and there is evidence that this contributes to tumor progression. The causes and consequences of this epigenetic disruption remain however unclear.
Charles De Smet and his group discovered that alterations of DNA methylation often affect a particular group of genes, which normally display specific expression in germline cells (especially those at the origin spermatozoids in males). These genes loose methylation in many tumors, and become therefore aberrantly activated. Due to their particular expression profile, such genes were termed “cancer-germline” (CG).
Current studies in the lab aim at identifying the mechanisms that lead to loss of methylation and activation of CG genes in tumors. Further efforts are focused on the identification of genes other than CG genes that also undergo epigenetic activation in cancer. To these ends, researchers in the team rely largely on bioinformatics approaches, which allow large-scale analysis of genomes and epigenomes.
Through the identification of epigenetically altered genes, the objective is to uncover new mechanisms of tumor development. Another goal is to search for early biomarkers of the disease.