Transcriptome analysis stratifies second-generation non-WNT/non-SHH medulloblastoma subgroups into clinically tractable subtypes

AbstractMedulloblastoma (MB), one of the most common malignant pediatric brain tumor, is a heterogenous disease comprised of four distinct molecular groups (WNT, SHH, Group 3, Group 4). Each of these groups can be further subdivided into second-generation MB (SGS MB) molecular subgroups, each with distinct genetic and clinical characteristics. For instance, non-WNT/non-SHH MB (Group 3/4) can be subdivided molecularly into eight distinct and clinically relevant tumor subgroups. A further molecular stratification/summarization of these SGS MB would allow for the assignment of patients to risk-associated treatment protocols. Here, we performed DNA- and RNA-based analysis of 574 non-WNT/non-SHH MB and analyzed the clinical significance of various molecular patterns within the entire cohort and the eight SGS MB, with the aim to develop an optimal risk stratification of these tumors. Multigene analysis disclosed several survival-associated genes highly specific for each molecular subgroup within this non-WNT/non-SHH MB  cohort with minimal inter-subgroup overlap. These subgroup-specific and prognostically relevant genes were associated with pathways that could underlie SGS MB clinical-molecular diversity and tumor-driving mechanisms. By combining survival-associated genes within each SGS MB, distinct metagene set s being appropriate for their optimal risk stratification were identified. Defined subgroup-specific metagene sets were independent variables in the multivariate models g...
Source: Acta Neuropathologica - Category: Neurology Source Type: research