CpG hypermethylation and WNT/AP-1 cooperativity define the epigenetic landscape and a clinical subgroup of high-risk pediatric adrenocortical carcinoma.

CpG island hypermethylation and WNT/AP-1 activation define a high-risk subgroup with poor prognosis in pediatric adrenocortical carcinoma.

• Why it matters: Understanding the molecular features of these tumors is crucial for improving risk stratification and developing targeted therapies for this rare and aggressive cancer.
• What they did: The study integrated DNA methylation, transcriptomics, chromatin accessibility, and spatial analysis of 214 tumors, identifying four risk groups and characterizing the high-risk subgroup’s epigenetic and transcriptional landscape.
• The result: Findings reveal potential therapeutic targets, such as entinostat, which reverses methylation and inhibits tumor growth, paving the way for personalized treatment strategies in pediatric adrenocortical carcinoma.