DNA-methylation profiling discloses significant advantages over NanoString method for molecular classification of medulloblastoma

Excerpt

It is well known that the histological entity medulloblastoma (MB) comprises distinct molecular subgroups. According to the current international consensus, four main molecular MB subgroups (WNT; SHH, Group 3 and Group 4) with divergent biology and clinical outcomes were outlined [4, 5]. More recently, the 2016 WHO classification for CNS tumors additionally recognized that it is of clinical relevance to distinguish TP53 wild type from TP53 mutant SHH-MB [3, 6]. Therefore, a method for accurate and reproducible molecular subgrouping of routinely prepared FFPE MB specimens is very important for patient stratification in a clinical setting. Recently, two main methods with compatible expenses have been applied for these purposes in routine practice: (1) the RNA-based NanoString method applying a CodeSet of 22 discriminatory genes [2] and (2) DNA-based methylation profiling applying Illumina Infinium HumanMethylation450/EPIC BeadChip arrays [1]. When comparing both methods, DNA-methylation profiling revealed some methodological advantages including a superior stability of DNA compared with RNA and the fact that from this platform genome-wide cytogenetic profiles can be derived in addition to the methylation profiles to identify DNA copy number aberrations at a reasonable solution comparable to array CGH [1, 4]. …