From Cancer-Testis genes to Cancer-Testis enhancers

Author(s): Julie Devis,Axelle Loriot,Charles De Smet,Laurent Gatto

Affiliation(s): UCLouvain



Cancer-Testis (CT) genes are normally expressed only in germ cells and not in healthy somatic tissues. However, they are aberrantly activated in many tumours. Many CT genes are regulated by methylation. Their promoters are highly methylated in all healthy somatic tissues and demethylated in germ cells. They are also demethylated in tumours in which they are activated. This is a consequence of the global demethylation process often observed in cancer. These characteristics give them clinical potential, as they produce cancer-specific antigens and can thus be used as target for cancer immunotherapy. We have recently developed the CTexploreR Bioconductor package, an updated database for CT genes. Promoters are not the only regulatory regions that can be affected by DNA methylation. It has been shown that many enhancers, that are activating distal regulatory regions, can be methylated. Their methylation can be altered in tumours, affecting the expression of their target genes. We hence wondered if we could find CT enhancers that would behave like CT genes promoters. We compared ENCODE cis-regulatory elements and whole genome bisulfite-seq data in somatic and germinal healthy tissues and in cancer to find enhancers that are active and demethylated exclusively in germ cells and tumours. We identified CT-like enhancer candidates that will be further defined.