Impact of 5-azacytidine on DNA methylation and gene expression in ACC cell lines

Adrenocortical carcinomas (ACCs) are rare and aggressive endocrine cancers of the adrenal gland. Recently, a subtype of ACC characterized by a CpG island methylator phenotype (CIMP), associated with especially poor diagnosis, has been discovered. The purpose of this study is to investigate the role of DNA methylation and the impact on demethylating agent 5-azacytidine in ACC tumors aggressiveness. To this aim, we generated RRBS and RNAseq data from two ACC and one non-tumour cell lines treated or not with 5-azacytidine. We showed that CIMP has a direct impact on the aggressiveness of tumors through two main mechanisms; (1) by increasing survival and proliferation and (2) by favoring the tumor immune escape. These two mechanisms could at least partially be reversed upon 5-azacytidine treatment. Overall, our results show that strongly suggest that the co-treatment with demethylating agents to enhance the efficacy of immunotherapy could be beneficial for patients with high CIMP ACC. Overall design: Examination of DNA methylation by RRBS and transcriptome by RNA-seq in the two ACC cell lines, H295R and MUC-1, and the non tumor cell line HUVEC, treated or not with 5µM 5-azacytidine