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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Cytogenetic analyses in 81 patients with brain gliomas: correlation with clinical outcome and morphological data
Filip Kramar1, Zuzana Zemanova, Kyra Michalova
1Department of Neurosurgery, 1st Faculty of Medicine, Charles University and Central Military Hospital, Prague 16902, Czech Republic. filip.kramar@uvn.cz
Abstract:
Specific gene mutations, loss of heterozygosity, deletions and/or amplifications of entire chromosomal regions and gene silencing have been described in gliomas. 82 samples from 81 patients were investigated to detect the deletion of TP53, RB1, CDKN2A genes, deletion of 1p36 and 19q13.3 region, amplification of EGFR gene, trisomy of chromosome 7 and monosomy of chromosome 10 in glial cells. Dual-colour interphase fluorescence in situ hybridization (I-FISH) with locus-specific and/or chromosome enumeration DNA probes were used for cytogenetic analyses. In the study, molecular cytogenetic analyses were successfully performed in 74 patients (91.3%) and were uninformative in 7 only (8.7%). The cytogenetic analyses were correlated with morphological data and clinical outcome. I-FISH was the essential part of diagnostics. In comparison with the clinical data, the patients' age seems to be a factor more important for the overall survival, rather than cytogenetic findings in glial tumours. The combined deletion of 1p36 and 19q13.3 chromosomal regions predicts longer overall survival for patients with oligodendroglial tumours.
Insights
This study investigated genetic alterations in glioma patients using molecular cytogenetics. Combined deletion of 1p36 and 19q13.3 regions predicts longer survival in oligodendroglial tumors.
Area of Science:
- Neuro-oncology
- Molecular Genetics
- Cytogenetics
Background:
- Gliomas exhibit diverse genetic alterations, including gene mutations, deletions, amplifications, and silencing.
- Accurate molecular and cytogenetic profiling is crucial for glioma diagnosis and prognosis.
Purpose of the Study:
- To investigate specific genetic alterations (TP53, RB1, CDKN2A deletions; 1p36/19q13.3 deletions; EGFR amplification; chromosome 7 trisomy; chromosome 10 monosomy) in glioma samples.
- To correlate cytogenetic findings with morphological data and clinical outcomes, particularly overall survival.
Main Methods:
- Dual-color interphase fluorescence in situ hybridization (I-FISH) was employed for cytogenetic analyses.
- Locus-specific and chromosome enumeration DNA probes were utilized.
- Molecular cytogenetic analyses were performed on 82 samples from 81 patients, with successful analysis in 91.3%.
Main Results:
- I-FISH proved to be an essential diagnostic tool.
- Patient age was identified as a more significant factor for overall survival than most cytogenetic findings in gliomas.
- Combined deletion of the 1p36 and 19q13.3 chromosomal regions was associated with longer overall survival in oligodendroglial tumor patients.
Conclusions:
- Molecular cytogenetics, particularly I-FISH, plays a vital role in glioma diagnostics.
- While age is a key prognostic factor, specific cytogenetic markers like combined 1p36/19q13.3 deletion offer prognostic value for oligodendroglial tumors.