Risk Stratification of Childhood Medulloblastoma Using Integrated Diagnosis: Discrepancies with Clinical Risk Stratification

Abstract

Background Recent genomic studies identified four discrete molecular subgroups of medulloblastoma (MB), and the risk stratification of childhood MB in the context of subgroups was refined in 2015. In this study, we investigated the effect of molecular subgroups on the risk stratification of childhood MB. Methods The nCounter® system and a customized cancer panel were used for molecular subgrouping and risk stratification in archived tissues. Results A total of 44 patients were included in this study. In clinical risk stratification, based on the presence of residual tumor/metastasis and histological findings, 24 and 20 patients were classified into the average-risk and high-risk groups, respectively. Molecular subgroups were successfully defined in 37 patients using limited gene expression analysis, and DNA panel sequencing additionally classified the molecular subgroups in three patients. Collectively, 40 patients were classified into molecular subgroups as follows: WNT (n = 7), SHH (n = 4), Group 3 (n = 8), and Group 4 (n = 21). Excluding the four patients whose molecular subgroups could not be determined, among the 17 average-risk group patients in clinical risk stratification, one patient in the SHH group with the TP53 variant was reclassified as very-high-risk using the new risk classification system. In addition, 5 out of 23 patients who were initially classified as high-risk group in clinical risk stratification were reclassified into the low- or standard-risk groups in the new risk classification system. Conclusion The new risk stratification incorporating integrated diagnosis showed some discrepancies with clinical risk stratification. Risk stratification based on precise molecular subgrouping is needed for the tailored treatment of MB patients.

Liquid Biopsies for Monitoring Medulloblastoma: Circulating Tumor DNA as a Biomarker for Disease Progression and Treatment Response

“…Liquid biopsies have demonstrated effectiveness in the monitoring and prediction of disease progression in diffuse midline gliomas (DMGs) and medulloblastomas (MBs) [ 86 ]. Genomic analyses have delineated prognostically significant molecular subgroups [ 89 ]. There is evidence that highlighted the identification of ctDNA alterations in the CSF of 97.3% of glioma cases [ 33 ].…”