Methylation profiling of plasma cell-free DNA in pediatric brain tumor patients

Using cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), we analyzed methylation profiles in 93 plasma samples from 77 pediatric brain tumor patients and 16 non-neoplastic patients. Binomial GLMnet classifiers of tumor and tumor subtypes were built in training sets, and performance was evaluated in test sets. The methylation profiles from plasma cfMeDIP-seq discriminated tumor from non-tumor patients with 0.83 accuracy (precision = 0.93, sensitivity = 0.86, and specificity = 0.67). Among major tumor subtypes vs. nontumors, circumscribed astrocytic glioma showed an accuracy of 0.86 (precision = 0.88, sensitivity = 0.88, and specificity = 0.83), and glioneuronal tumors had an accuracy of 0.83 (precision, sensitivity, and specificity = 0.83). Circumscribed astrocytic glioma and glioneuronal tumors could be discriminated from other tumor subtypes with 0.79 and 0.82 accuracy, respectively. Overall design: We analyzed methylation profiles in 93 plasma samples from 77 pediatric brain tumor patients and 16 non-neoplastic patients. Binomial GLMnet classifiers of tumor and tumor subtypes were built in training sets, and performance was evaluated in test sets.