Mechanisms involved in DNA demethylation and activation of cancer-germline genes in human tumors

Many human tumors are characterized by the aberrant activation of genes that are expressed specifically in the germline. These genes, called “cancer-germline” genes (or “CG” genes), are interesting because they produce tumor-specific antigens, and because some of them have an oncogenic role. The purpose of my thesis was to investigate the mechanisms leading to the activation of CG genes in tumors, and more particularly in melanoma. In a first step, we demonstrated the predominant role of DNA demethylation compared to histone modifications for CG gene activation. We then tried to find the trigger of this DNA demethylation. Our transcriptomic analyses and cellular models have allowed us to identify a gene expression signature that attributes the cause of CG gene demethylation in melanoma to a transient depletion of DNMT1, the enzyme responsible for the maintenance of DNA methylation in cells.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201