DNA Methylation Profiling Reveals Prognostically Significant Groups in Pediatric Adrenocortical Tumors: A Report From the International Pediatric Adrenocortical Tumor Registry

Pediatric adrenocortical carcinomas (ACCs) are aggressive; the overall survival of pediatric patients with ACCs is 40%-50%. Appropriate staging and histologic classification are crucial as children with incompletely resected tumors or metastatic disease have a dismal prognosis. The clinical course of pediatric adrenocortical tumors (ACTs) is difficult to predict using the current classification schemas, which rely heavily on subjective microscopic and gross macroscopic variables. Recent advances in adult ACT studies have revealed distinct DNA-methylation patterns with prognostic significance that have not been systematically interrogated in the pediatric population. We performed DNA-methylation analyses on 48 newly diagnosed ACTs from the International Pediatric Adrenocortical Tumors Registry (IPACTR) and 12 pediatric adrenal controls to evaluate for distinct methylation groups. Pediatric methylation data were also compared systematically to the adult ACC cohort from The Cancer Genome Atlas (TCGA).