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Updated: Mar 15, 2026
Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
Clinicopathological characteristics, molecular subgrouping, and expression of miR-379/miR-656 cluster (C14MC) in
Kavneet Kaur1, Aanchal Kakkar1, Anupam Kumar1
1Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Abstract:
Medulloblastoma (MB) is a childhood tumor comprising four molecular subgroups: WNT, SHH, group 3 and group 4, with diagnostic and prognostic connotations. Very few studies are available on molecular subgrouping of adult MBs due to their rarity. Recently, loss of chromosome14q has been reported in SHH MBs, with downregulation of miR-379/miR-656 cluster (C14MC) in pediatric SHH MBs. Hence, the present study on adult MBs was undertaken to enumerate clinicopathological characteristics and molecular subgroups, and to analyze expression of C14MC and its transcriptional regulators, MEF2, JUN and ESRRG. Immunohistochemistry for β-catenin, GAB1 and YAP1 was performed to identify molecular subgroups. MYC amplification was evaluated by FISH. Expression profiling of 47 miRNAs from C14MC was performed using customized Taqman low-density array. Expression of transcriptional regulators was examined using RT-PCR. Seventy-one adult MBs were analyzed. They had male predominance and majority were located laterally (52 %). A significant proportion of cases were of Desmoplastic/nodular histology (32 %); MBEN was not seen. WNT tumors constituted 4.2 %, SHH 62 %, and non-WNT/non-SHH 33.8 %. MYC amplification was identified in 11.1 % cases. Patient outcome was worse in adults. Significant downregulation of C14MC was observed in all MB subgroups, and MEF-2 expression was downregulated. Adult MBs are distinct from childhood MBs in terms of location, histopathological subtypes, molecular subgroups, as well as prognosis. Silencing of C14MC in all MB subgroups suggests its role as a tumor suppressor locus in tumorigenesis. Deregulation of C14MC can possibly be attributed to repression of MEF2.
Insights
Adult medulloblastoma (MB) differs from pediatric MB, with SHH subgroup prevalence and worse outcomes. The miR-379/miR-656 cluster (C14MC) is downregulated across all adult MB subgroups, suggesting a tumor suppressor role.
Area of Science:
- Neuro-oncology
- Molecular Diagnostics
- Genetics
Background:
- Medulloblastoma (MB) is a pediatric brain tumor with four molecular subgroups (WNT, SHH, group 3, group 4).
- Adult MB is rare, limiting studies on its distinct molecular characteristics and prognosis.
- Previous research noted chromosome 14q loss and C14MC downregulation in pediatric SHH MB.
Purpose of the Study:
- To characterize adult MB clinicopathological features and molecular subgroups.
- To investigate the expression of the C14MC miRNA cluster and its regulators (MEF2, JUN, ESRRG) in adult MB.
- To compare adult MB with pediatric MB.
Main Methods:
- Immunohistochemistry for β-catenin, GAB1, and YAP1 to define molecular subgroups.
- Fluorescence in situ hybridization (FISH) for MYC amplification.
- Customized Taqman low-density array for C14MC miRNA expression profiling.
- RT-PCR for transcriptional regulator expression.
Main Results:
- Seventy-one adult MB cases analyzed, showing male predominance and lateral location.
- SHH subgroup was predominant (62%), with significant Desmoplastic/nodular histology (32%).
- C14MC was significantly downregulated in all adult MB subgroups, alongside MEF-2 downregulation.
Conclusions:
- Adult MB exhibits distinct features from pediatric MB, including location, histology, molecular subgroups, and poorer prognosis.
- The widespread downregulation of C14MC suggests its function as a tumor suppressor in medulloblastoma.
- MEF2 repression may contribute to C14MC deregulation in adult MB.
