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Published on: January 9, 2019
Loss of heterozygosity of TRIM3 in malignant gliomas
Jean-Louis Boulay1, Urs Stiefel, Elisabeth Taylor
1Department of Biomedicine, University Hospital, Basel, Switzerland. Jean-Louis.Boulay@unibas.ch
Background:
Malignant gliomas are frequent primary brain tumors associated with poor prognosis and very limited response to conventional chemo- and radio-therapies. Besides sharing common growth features with other types of solid tumors, gliomas are highly invasive into adjacent brain tissue, which renders them particularly aggressive and their surgical resection inefficient. Therefore, insights into glioma formation are of fundamental interest in order to provide novel molecular targets for diagnostic purposes and potential anti-cancer drugs. Human Tripartite motif protein 3 (TRIM3) encodes a structural homolog of Drosophila brain tumor (brat) implicated in progenitor cell proliferation control and cancer stem cell suppression. TRIM3 is located within the loss of allelic heterozygosity (LOH) hotspot of chromosome segment 11p15.5, indicating a potential role in tumor suppression.
Methods:
Here we analyze 70 primary human gliomas of all types and grades and report somatic deletion mapping as well as single nucleotide polymorphism analysis together with quantitative real-time PCR of chromosome segment 11p15.5.
Results:
Our analysis identifies LOH in 17 cases (24%) of primary human glioma which defines a common 130 kb-wide interval within the TRIM3 locus as a minimal area of loss. We further detect altered genomic dosage of TRIM3 in two glioma cases with LOH at 11p15.5, indicating homozygous deletions of TRIM3.
Conclusion:
Loss of heterozygosity of chromosome segment 11p15.5 in malignant gliomas suggests TRIM3 as a candidate brain tumor suppressor gene.
Insights
Loss of heterozygosity (LOH) in chromosome 11p15.5 suggests the Tripartite motif protein 3 (TRIM3) gene may act as a brain tumor suppressor. This finding could lead to new diagnostic targets for malignant gliomas.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Molecular Biology
Background:
- Malignant gliomas are aggressive brain tumors with poor prognosis and limited treatment efficacy.
- Glioma invasiveness complicates surgical resection and necessitates novel therapeutic targets.
- Human Tripartite motif protein 3 (TRIM3) is a homolog of Drosophila brain tumor (brat) and may function as a tumor suppressor.
Purpose of the Study:
- To investigate the role of TRIM3 in malignant glioma development.
- To identify potential tumor suppressor genes within the 11p15.5 chromosomal region.
Main Methods:
- Analysis of 70 primary human gliomas of all grades.
- Somatic deletion mapping and single nucleotide polymorphism analysis of chromosome segment 11p15.5.
- Quantitative real-time PCR to assess TRIM3 gene dosage.
Main Results:
- Loss of heterozygosity (LOH) at 11p15.5 was identified in 24% of gliomas.
- A common 130 kb minimal region of loss within the TRIM3 locus was defined.
- Homozygous deletions of TRIM3 were detected in two glioma cases with LOH.
Conclusions:
- Loss of heterozygosity in chromosome segment 11p15.5 suggests TRIM3 is a candidate brain tumor suppressor gene.
- TRIM3 alterations may contribute to malignant glioma pathogenesis.
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