Association of loss of heterozygosity with shorter survival in primary glioblastoma patients.

Loss of heterozygosity (LOH) co-deletion 1p/19q, MGMT promoter methylation and/or IDH1 mutation generally signify a better prognosis for patients with glioma. However, the influence of 1p/19q co-deletion and the LOH on other chromosomes in primary glioblastoma on survival is still debatable. The aim of our study was to identify LOH on chromosomes 1p, 19q, 9p, 10q, 13q, and 17p, and evaluate their impact either alone or 1p/19q co-deletion or by groups of LOH on the overall survival of 42 primary glioblastoma patients without an oligodendroglial component. These patients were additionally molecularly characterized for EGFR amplification, IDH1 mutations and TP53 mutations. We assessed their influence on the overall survival of glioblastoma patients. LOH in at least one of the loci on all examined chromosomes was detected in 65% of cases and was significantly associated with shorter overall survival (hazard ratio 3.07; 95% CI: 1.29-7.31, p = 0.006). 1p/19q co-deletion was infrequent (7.14%) and had no impact on overall survival. Our results indicate that in primary glioblastoma a specific LOH group analysis may be important for the prognosis. LOH 1p/19q co-deletion is rare in glioblastoma without an oligodendroglial component and has no impact on patient survival.

Molecular analysis of chromosome 1, 10 and 19 abnormalities in human oligodendroglial tumors: relationship between frequency of LOH grade, age and gender.

BACKGROUND: Loss of heterozygosity (LOH) on 1p and 19q is observed in most oligodendroglial tumors. LOH on 10q appears to be less common in these tumors as compared to other gliomas. PATIENTS AND METHODS: We reviewed 14 patients with oligodendroglial tumors (10 low-grade and 4 anaplastic oligodendroglioma) to evaluate the frequency of LOH on 1p, 10q and 19q and correlate it with tumor grade and patients' age and gender; 5 loci on 1p and 5 on 19q as well as 4 on 10q were analyzed for LOH using PCR techniques. RESULTS: LOH on 1p together with 19q was detected in 6 tumors, 1 tumor showed deletion of 19q accompanied with deletion on 10q. Deletion on 1p was associated with deletion of 19q (p < 0.005) and mutual associations among deletions at loci on 19q (p < 0.05) were found. Patients with LOH on 1p were younger on average than patients with retained heterozygosity (p = 0.05). Grade II oligodendrogliomas predominated among younger patients (p < 0.01) while grade III oligodendrogliomas predominated among women (p < 0.005). No association between LOH on 1p nor 19q and tumor grade or patients' gender was found. CONCLUSION: Our study provides several clinically interesting findings and further supports the hypothesis of chromosome 1p and 19q involvement in the oligodendroglial cancerogenesis.

Gene-specific modulation of RNA synthesis and degradation by extremely low frequency electromagnetic fields.

Pulse-labeling studies from our laboratory and others have shown that extremely low frequency (ELF) electromagnetic fields can produce a transient increase in gene transcription. In this study, the synthesis, degradation and processing, and steady state levels of specific RNA species during exposure to ELF radiation were determined in human leukemia HL-60 cells. The overall steady state RNA levels, assessed by continuous and equilibrium labeling with 3H-uridine, were not affected by ELF exposure. Northern blot analysis using probes specific for c-myc, beta-actin, and 45S ribosomal RNA gene products revealed that ELF did not alter the steady state levels of these RNAs. Examination of gene-specific transcription by a novel nuclease protection assay revealed that while ELF did not substantially alter the transcription rates for c-myc and beta-actin, transcription of the 45S ribosomal RNA gene was increased by 40-50%. To explain the observed increase in the synthesis of 45S ribosomal RNA without an associated increase in its steady state level, the degradation and processing of the ribosomal gene transcript in the presence and absence of an ELF field were followed by pulse-chase 3H-uridine labeling. This revealed that ELF radiation accelerated both the processing and degradation of the ribosomal RNA transcript. During ELF exposure, the half-life of the 45S ribosomal RNA was decreased from 115 min. to 85 min. These results show that ELF can selectively affect RNA levels by modulating either the transcription rate and/or RNA post-transcriptional processing and turnover.

Delineation of electric and magnetic field effects of extremely low frequency electromagnetic radiation on transcription.

The relative effects of the electric and magnetic field components of extremely low frequency electromagnetic radiation (ELF) on transcription were examined in human leukemia HL-60 cells. Delineation of the individual field contributions was achieved by irradiating cells in separate concentric compartments of a culture dish within a solenoid chamber. This exposure system produced a homogeneous magnetic field with a coincident electric field whose strength varied directly with distance from the center of the culture dish. Irradiation of HL-60 cells with sine wave ELF at 60 Hz and a field strength of 10 Gauss produced a transient increase in the transcriptional rates which reached a maximum of 50-60% enhancement at 30-120 minutes of irradiation and declined to near basal levels by 18 hours. Comparison of transcription responses to ELF of cells in different concentric compartments revealed that the transcriptional effects were primarily the result of the electric field component with little or no contribution from the magnetic field.