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ASPM gene expression in medulloblastoma
Tânia M Vulcani-Freitas1, Najsla Saba-Silva, Andréa Cappellano
1Institute of Pediatric Oncology, Pediatric Department, Federal University of São Paulo, São Paulo, Brazil.
Purpose:
Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features.
Methods:
Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival.
Results:
All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters.
Conclusion:
ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.
Insights
The ASPM gene is overexpressed in pediatric medulloblastoma, a common childhood brain tumor. This finding suggests ASPM may be a potential therapeutic target, though no clinical associations were found in this study.
Area of Science:
- Neuro-oncology
- Developmental neurobiology
- Cancer genetics
Background:
- Medulloblastomas are common pediatric central nervous system malignant tumors, often treated aggressively with significant side effects.
- Current treatments like chemotherapy and radiotherapy lack specificity, necessitating novel therapeutic strategies.
- The ASPM gene, implicated in glioblastoma, shows potential as a molecular target due to its role in cell proliferation.
Purpose of the Study:
- To investigate ASPM gene expression in medulloblastoma samples.
- To correlate ASPM expression levels with clinical features of pediatric medulloblastoma patients.
Main Methods:
- Gene expression analysis using quantitative PCR (qPCR) with SYBR Green in 37 pediatric medulloblastoma samples.
- Statistical analysis including t-tests, Mann-Whitney tests, and Kaplan-Meier survival analysis.
Main Results:
- All analyzed medulloblastoma samples exhibited significant overexpression of the ASPM gene (over 40-fold).
- No statistically significant association was identified between ASPM overexpression and the clinical parameters of the patients.
Conclusions:
- ASPM overexpression may disrupt neural stem cell differentiation during central nervous system development.
- This disruption potentially contributes to the pathogenesis of medulloblastoma, a tumor originating from embryonic cerebellar progenitor cells.
