			Home About us Contact

Oligodendroglial Tumors (oligodendroglial + tumor)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Oncology & Radiotherapy	50%
Pathology	33%

Selected Abstracts

Oligodendroglial Tumors: Refinement of Candidate Regions on Chromosome Arm 1p and Correlation of 1p/19q Status with Survival

BRAIN PATHOLOGY, Issue 2 2004
Jörg Felsberg
Loss of heterozygosity (LOH) on the chromosome arms 1p and 19q is frequent in oligodendroglial tumors and has been correlated with chemosensitivity and good prognosis in anaplastic oligodendrogliomas. The oligodendroglioma-associated tumor suppressor genes on 1p and 19q are as yet unknown. To narrow down candidate regions on 1p, we investigated oligodendroglial tumors from 89 patients for LOH at up to 30 polymorphic loci on 1p. In addition, all tumors were studied for LOH at 7 loci on 19q. Combined LOH on 1p and 19q was detected in 20 (83%) of 24 oligodendrogliomas, 15 (63%) of 24 anaplastic oligodendrogliomas, 10 (56%) of 18 oligoastrocytomas, and 12 (52%) of 23 anaplastic oligoastrocytomas. Five tumors demonstrated partial deletions on 1p, which allowed to define 3 distinct candidate regions at 1 p36.31 -pter distal to D1S2633, 1p36.22-p36.31 between D1S489 and D1S2642, and 1p34.2-p36.1 between D1S2743 and D1S482, respectively. No partial deletions were detected on 19q. Combined LOH on 1p and 19q was associated with prolonged time to progression (TTP), longer overall survival (OS), and a higher 5-year survival rate. Depending on the presence or absence of combined LOH on 1p and 19q, patients with anaplastic oligodendroglial tumors treated with adjuvant radio- and/or chemotherapy showed a median TTP of 86 months versus 39 months, a median OS of 91 months versus 46 months, and a 5-year survival rate of 80% versus 36%, respectively. Similarly, LOH on 1p and 19q was associated with longer survival in patients with low-grade oligodendroglial tumors (TTP: 57 months versus 47 months; OS: 172 months versus 105 months; 5-year survival rate: 92% versus 70%). Thus, our results refine the location of putative oligodendroglioma suppressor genes on 1p and support the significance of LOH on 1p and 19q as a favorable prognostic marker. [source]

Characterization of oligodendrogliomas using short echo time 1H MR spectroscopic imaging

NMR IN BIOMEDICINE, Issue 1 2003
M. Rijpkema
Abstract Oligodendroglial tumors may not be distinguished easily from other brain tumors based on clinical presentation and magnetic resonance imaging (MRI) alone. Identification of these tumors however may have therapeutic consequences. The purpose of this study was to characterize and identify oligodendrogliomas by their metabolic profile as measured by 1H MR spectroscopic imaging (MRSI). Fifteen patients with oligodendroglial tumors (eight high-grade oligodendrogliomas, seven low-grade oligodendrogliomas) underwent MRI and short echo time 1H MRSI examinations. Five main metabolites found in brain MR spectra were quantified and expressed as ratios of tumor to contralateral white matter tissue. The level of lipids plus lactate was also assessed in the tumor. For comparison six patients with a low grade astrocytoma were also included in the study. The metabolic profile of oligodendrogliomas showed a decreased level of N -acetylaspartate and increased levels of choline-containing compounds and glutamine plus glutamate compared with white matter. The level of glutamine plus glutamate was significantly higher in low-grade oligodendrogliomas than in low-grade astrocytomas and may serve as a metabolic marker in diagnosis and treatment planning. In high-grade oligodendrogliomas large resonances of lipids plus lactate were observed in contrast to low-grade tumors. Copyright © 2003 John Wiley & Sons, Ltd. [source]

EMP3 overexpression is associated with oligodendroglial tumors retaining chromosome arms 1p and 19q

INTERNATIONAL JOURNAL OF CANCER, Issue 4 2007
Kay Ka Wai Li
Abstract The epithelial membrane protein 3 (EMP3) gene located on chromosome 19q13 has been implicated as a candidate tumor suppressor gene (TSG) in neuroblastomas and gliomas. The aim of this study was to investigate whether EMP3 is involved in oligodendroglial tumors (OTs), which frequently carry combined chromosomes 1p and 19q deletion. We first investigated the transcript level of EMP3 in a cohort of 57 OTs by quantitative real-time RT-PCR. Our results showed that 10 (18%) tumors had reduced EMP3 expression level compared to normal brains. Six of these tumors carried chromosome 19q13 deletion but no statistical correlation was found between the 2 parameters. Intriguingly, a similar proportion (11 of 57, 19%) of tumors displayed EMP3 overexpression, with 8 of them having transcript level >10-fold higher than normal brain. All 11 OTs retained chromosomes 1p36 and 19q13, and a significant association was found between EMP3 overexpression and balanced chromosomes 1p36 and 19q13 (p = 0.004). The methylation status of EMP3 was evaluated by bisulfite sequencing in 29 OTs with diverse expression levels. All tumors except 3 showed aberrant methylation of EMP3 and no correlation was observed between transcript level and methylation status, suggesting that methylation alone does not mediate transcriptional down-regulation of EMP3 in OTs. In conclusion, our study demonstrates that EMP3 overexpression is involved in OTs retaining chromosomes 1p and 19q and does not support EMP3 as the target TSG on chromosome 19q13 in OTs. © 2006 Wiley-Liss, Inc. [source]

Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2005
Maria Möllemann
Abstract Allelic losses on the chromosome arms 1p and 19q have been associated with favorable response to chemotherapy and good prognosis in anaplastic oligodendroglioma patients, but the molecular mechanisms responsible for this relationship are as yet unknown. The DNA repair enzyme O6 -methylguanine DNA methyltransferase (MGMT) may cause resistance to DNA-alkylating drugs commonly used in the treatment of anaplastic oligodendrogliomas and other malignant gliomas. We report on the analysis of 52 oligodendroglial tumors for MGMT promoter methylation, as well as mRNA and protein expression. Using sequencing of sodium bisulfite-modified DNA, we determined the methylation status of 25 CpG sites within the MGMT promoter. In 46 of 52 tumors (88%), we detected MGMT promoter hypermethylation as defined by methylation of more than 50% of the sequenced CpG sites. Real-time reverse transcription-PCR showed reduced MGMT mRNA levels relative to non-neoplastic brain tissue in the majority of tumors with hypermethylation. Similarly, immunohistochemical analysis showed either no or only small fractions of MGMT positive tumor cells. MGMT promoter hypermethylation was significantly more frequent and the percentage of methylated CpG sites in the investigated MGMT promoter fragment was significantly higher in tumors with loss of heterozygosity on chromosome arms 1p and 19q as compared to tumors without allelic losses on these chromosomes arms. Taken together, our data suggest that MGMT hypermethylation and low or absent expression are frequent in oligodendroglial tumors and likely contribute to the chemosensitivity of these tumors. [source]

Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors: A clinicopathological study using fluorescence in situ hybridization

NEUROPATHOLOGY, Issue 1 2007
Yoon Kyung Jeon
To verify the prognostic implications of the statuses of chromosome 1p and 19q and the expressions of p53, p16 and GFAP in oligodendrogliomas, we investigated these parameters and correlated the results with patient outcome. Twenty-seven cases of low-grade oligodendroglioma (LO) and 29 cases of anaplastic oligodendroglioma (AO) were analyzed by FISH for 1p and 19q status and by immunohistochemistry for p53, p16, and GFAP expression using a tissue microarray. Direct sequencing of the p53 gene was also performed. 1p deletion was observed in 39 of 56 patients (69.9%), and 19q deletion in 41 of 56 (73.2%). Combined loss of 1p and 19q was found in 38 of 56 (67.9%) and exhibited distinct concomitant deletion (P = 0.000). p53 overexpression was observed in 17 cases (30.3%), GFAP expression in 18 cases (32.1%), and p16 loss in 40 cases (74%) of oligodendrogliomas. The expressions of p53 and GFAP were more frequent in AO than in LO (P = 0.015 and 0.001). In contrast, p53 expression was more common in oligodendrogliomas with an intact 19q (P = 0.029), or an intact 1p (P = 0.071). Only five of 14 patients with p53 expression showed TP53 mutation, which was inversely correlated with 1p deletion (P = 0.036). Patients with combined loss of 1p and 19q exhibited better overall survival (P = 0.045). Patients with p53 expression without combined 1p and 19q loss showed poor overall survival (P < 0.000). However, TP53 mutation along with 1p and 19q status could not predict patient outcome. Patients with p16 loss without combined 1p and 9q loss showed poor overall survival (P = 0.011). Therefore, in oligodendrogliomas, the absence of the combined deletion of 1p and 19q and the aberrant expression of p53 or loss of p16 could be used as poor prognostic markers. [source]

Characterization of oligodendrogliomas using short echo time 1H MR spectroscopic imaging

Oligodendroglial Tumors: Refinement of Candidate Regions on Chromosome Arm 1p and Correlation of 1p/19q Status with Survival

Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features

CANCER, Issue 5 2003
M.D., Martin J. van den Bent Ph.D.
Abstract BACKGROUND Patients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy. METHODS The initial presentation, prior treatments, overall survival, and response to chemotherapy were assessed. The 1p and 19q status in OD lesions was determined with fluorescence in situ hybridization on paraffin embedded, archival material using locus specific probes. P53 mutations were assessed by polymerase chain reaction,single-strand conformation polymorphism analysis and immunohistochemistry for P53; the proliferation index was assessed with the MIB-1 antibody. RESULTS Patients who had OD lesions with a combined loss of 1p and 19q typically presented with low-grade tumors that manifested with seizures of long-standing duration. In contrast, patients who had OD lesions without a combined loss of 1p and 19q usually presented with focal deficits that required immediate treatment. Both the response rate to chemotherapy and the time to disease progression after chemotherapy were significantly better in patients who had a combined loss of 1p and 19. Tumors with classic OD morphology more often had a combined loss of 1p and 19q, although the genotype was better at identifying patients with chemoresponsive tumors. P53 mutations were observed in three tumors, none of which had a combined loss of 1p and 19q. CONCLUSIONS OD lesions with combined a loss of 1p and 19q have a more indolent nature compared with OD lesions that do not have these losses. Virtually all patients with these tumors present with low-grade tumors accompanied by seizures and remain stable for prolonged periods. Future trials must keep these tumor types apart. Cancer 2003;97:1276,84. © 2003 American Cancer Society. DOI 10.1002/cncr.11187 [source]

Genetic alterations and signaling pathways in the evolution of gliomas

CANCER SCIENCE, Issue 12 2009
Hiroko Ohgaki
Gliomas are the most common primary brain tumors. They account for more than 70% of all neoplasms of the central nervous system and vary considerably in morphology, location, genetic alterations, and response to therapy. Most frequent and malignant are glioblastomas. The vast majority (>90%) develops rapidly after a short clinical history and without evidence of a less malignant precursor lesion (primary or de novo glioblastoma). Secondary glioblastomas develop more slowly through progression from low-grade or anaplastic astrocytoma. These glioblastoma subtypes constitute distinct disease entities that affect patients of different age, develop through distinct genetic pathways, show different RNA and protein expression profiles, and may differ in their response to radio- and chemotherapy. Recently, isocitrate dehydrogenase 1 (IDH1) mutations have been identified as a very early and frequent genetic alteration in the pathway to secondary glioblastomas as well as that in oligodendroglial tumors, providing the first evidence that low-grade astrocytomas and oligodendrogliomas may share common cells of origin. In contrast, primary glioblastomas very rarely contain IDH1 mutations, suggesting that primary and secondary glioblastomas may originate from different progenitor cells, despite the fact that they are histologically largely indistinguishable. In this review, we summarize the current status of genetic alterations and signaling pathways operative in the evolution of astrocytic and oligodendroglial tumors. (Cancer Sci 2009; 100 2235,2241) [source]