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Genetic alterations in glioma and medulloblastoma
1Department of Pathology, Duke University Medical Center, Durham, North Carolina.
Abstract:
Multiple genetic changes take place during tumor development and progression. These genetic changes result in inactivation of tumor suppressor genes and activation of proto-oncogenes. Frequent genetic changes observed in gliomas are losses of chromosomal regions on 9p, 10q, 13q, 17p and on 22. Loss of 10q is seen in more than 80% of the glioblastoma multiforme (GBM) tumors suggesting the presence of a gene critical for GBM formation on this chromosome. Amplification of epidermal growth factor receptor gene and expression of platelet derived growth factor and fibroblast growth factor genes are also common among gliomas. The most common genetic abnormality found in medulloblastomas is loss of 17p. The C-myc gene is amplified in a few primary tumors, but the incidence of amplification is higher in medulloblastoma derived cell lines. These findings suggest that the same two genetic processes, gene amplification and regional chromosomal loss, which characterize other primitive childhood neuroectodermal tumors such as retinoblastoma and neuroblastoma are also important in medulloblastomas.
Insights
Genetic changes like chromosomal loss and gene amplification are key in brain tumor development. Loss of 10q is frequent in glioblastoma multiforme, indicating a critical gene
Area of Science:
- Neuro-oncology
- Cancer Genetics
- Molecular Biology
Background:
- Tumorigenesis involves genetic alterations, including tumor suppressor gene inactivation and proto-oncogene activation.
- Gliomas and medulloblastomas exhibit specific chromosomal abnormalities and gene amplifications.
- Glioblastoma multiforme (GBM) frequently shows 10q loss, suggesting a critical gene on this region.
Purpose of the Study:
- To identify common genetic changes in gliomas and medulloblastomas.
- To investigate the role of chromosomal losses and gene amplifications in brain tumor progression.
- To pinpoint potential genes critical for glioblastoma multiforme formation.
Main Methods:
- Analysis of genetic alterations in glioma and medulloblastoma tumor samples.
- Examination of chromosomal regions, including losses on 9p, 10q, 13q, 17p, and 22.
- Assessment of gene amplification, focusing on epidermal growth factor receptor (EGFR) and C-myc.
Main Results:
- Frequent chromosomal losses observed in gliomas include 9p, 10q, 13q, 17p, and 22.
- Loss of 10q is present in over 80% of GBM tumors.
- Epidermal growth factor receptor gene amplification and increased expression of platelet-derived growth factor and fibroblast growth factor genes are common in gliomas.
- Loss of 17p is the most prevalent genetic abnormality in medulloblastomas.
- C-myc gene amplification is observed, with higher incidence in medulloblastoma cell lines.
Conclusions:
- Chromosomal losses and gene amplifications are critical genetic processes in brain tumor development.
- A gene crucial for GBM formation may reside on chromosome 10q.
- Medulloblastomas share genetic mechanisms (gene amplification, chromosomal loss) with other primitive neuroectodermal tumors.