Molecular subgroups of adult medulloblastoma: a long-term single-institution study

Background. Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. Methods. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Results. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. Conclusions. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. The Agilent Whole Human Genome Oligo Microarray Kit, 4×44K (Gene Expression Omnibus accession no. GPL6480) was used for gene expression profiling of the samples (n ¼ 13). Data were extracted with Feature Extraction Software v10.7 (Agilent Technologies). Raw data were normalized by Quantile algorithm,Gene Spring Software v11.0 (Agilent Technologies). Genes with a fold change ≥2 and P,.05 were selected for further analysis. Pathway annotation was performed by Ingenuity Systems.