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Patient survival and microsatellite instability in gliomas by high-resolution fluorescent analysis
M Mizoguchi1, T Inamura, K Ikezaki
1Departments of Neurosurgery and Neuropathology, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
Deficient repair of nucleotide mismatches in the genome is considered a major factor in tumorigenesis. Such deficiency is evidenced by alterations in dinucleotide repeats of microsatellite sequences, specifically microsatellite instability (MSI) or replication errors. We investigated the frequency of MSI in human gliomas in terms of patient outcome. Frequency of MSI was estimated by examining five loci on chromosomes 2, 5, 10, 11, and 13 in 31 gliomas using high-resolution fluorescent microsatellite analysis. MSI was found at all loci in only 2 malignant gliomas (6.5%). MSI was detected at the D10S197 locus in 3 of 11 glioblastomas (27.2%) and 4 of 8 anaplastic astrocytomas (50%), while no MSI was detected in low-grade gliomas. Among patients with anaplastic astrocytoma, the 4 with MSI at D10S197 died from local recurrence less than 18 months after surgery, while 3 of the patients without MSI survived for more than 20 months. MSI at D10S197 may be a prognostic marker for patients with anaplastic astrocytomas.
Insights
Microsatellite instability (MSI), a DNA repair defect, is linked to brain tumors. In anaplastic astrocytomas, MSI at the D10S197 locus may predict a poorer patient outcome.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Deficient DNA mismatch repair is a key factor in tumorigenesis.
- Microsatellite instability (MSI), indicated by alterations in microsatellite sequences, is a hallmark of such deficiencies.
- MSI is frequently observed in various cancers, but its role in human gliomas requires further investigation.
Purpose of the Study:
- To determine the frequency of MSI in human gliomas.
- To evaluate the association between MSI and patient outcomes in glioma cases.
- To identify potential prognostic markers for glioma patients.
Main Methods:
- Analysis of MSI frequency across five specific microsatellite loci (chromosomes 2, 5, 10, 11, and 13).
- Utilized high-resolution fluorescent microsatellite analysis on a cohort of 31 human gliomas.
- Correlated MSI status at specific loci with patient survival and tumor grade.
Main Results:
- MSI was detected in only 2 out of 31 (6.5%) malignant gliomas across all examined loci.
- MSI was identified at the D10S197 locus in 27.2% of glioblastomas and 50% of anaplastic astrocytomas.
- No MSI was observed in low-grade gliomas; however, MSI at D10S197 was associated with significantly shorter survival in anaplastic astrocytoma patients.
Conclusions:
- MSI is not uniformly present across all high-grade gliomas but occurs at specific loci.
- The D10S197 locus shows a higher prevalence of MSI in glioblastomas and anaplastic astrocytomas.
- MSI at the D10S197 locus may serve as a valuable prognostic biomarker for patients diagnosed with anaplastic astrocytomas.