Comprehensive and Integrative Methylome Analysis Across Endocrine Tumors Harboring the CpG Island Methylator Phenotype (CIMP)

Abstract

Cancer cells are marked by deregulation of gene expression and genomic instability attributed to genetic mutations and epigenetic alterations that determine active and repressed chromatin. Among the epigenetic modifications, DNA methylation deregulation is a hallmark in cancer. Non-tumoral cells present genome-wide methylation, and hypomethylation in CpG islands (CGIs). In contrast, some cancer types present global genome hypomethylation and widespread CGI hypermethylation, which define the CpG Island Methylator Phenotype (CIMP). CIMP was described in a plethora of cancer types, including some endocrine tumors. The phenotype has shown to participate in the tumorigenic process and showed prognostic and predictive values. Some CIMP cancers have been shown to share common target loci and downstream pathways, however, these commonalities have not been explored across CIMP endocrine tumors. Genomic and epigenetic alterations have been extensively described among the endocrine tumors, but up to now an articulated wide-endocrine analysis still remains, especially encompassing endocrine CIMP cancers and regulatory elements (besides CGIs). Therefore, the aim of this study is to search for epigenomic signatures associated to CIMP endocrine tumors and integrate our findings with other molecular and clinical available data.Key-words: endocrine tumors, hypermethylation, CIMP cancer.