Pathway Implications of Aberrant Global Methylation in Adrenocortical Cancer

CONTEXT: Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options. OBJECTIVE: Understanding of the molecular pathogenesis of this disease has been aided by genomic analyses highlighting alterations in TP53, WNT, and IGF signaling pathways. Further elucidation is needed to reveal therapeutically actionable targets in ACC. DESIGN: In this study, global DNA methylation levels were assessed by the Infinium HumanMethylation450 BeadChip Array on 18 ACC tumors and 6 normal adrenal tissues. A new, non-linear correlation approach, the discretization method, assessed the relationship between DNA methylation/gene expression across ACC tumors. RESULTS: This correlation analysis revealed epigenetic regulation of genes known to modulate TP53, WNT, and IGF signaling, as well as silencing of the tumor suppressor MARCKS, previously unreported in ACC. CONCLUSIONS: DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors.