Disease relevance of Oligodendroglioma

• In vivo, gene transfer of PDGF to neural progenitors induced the formation of oligodendrogliomas in about 60% of mice by 12 wk of age; PDGF transfer to astrocytes induced the formation of either oligodendrogliomas or mixed oligoastrocytomas in about 40% of mice in the same time period [1].
• In vivo infection of mice with retrovirus expressing PDGF and the p190 GAP domain caused a decreased incidence of oligodendrogliomas compared with that observed with PDGF alone [2].
• Our analysis of telomerase activity in 90 human gliomas showed that 19 of 19 oligodendrogliomas and 38 of 51 glioblastoma multiformes have detectable telomerase activity [3].
• Other tumor types found in BRCA1 mutation/haplotype carriers included prostatic, pancreas, skin, and lung cancer, a malignant melanoma, an oligodendroglioma, and a carcinosarcoma [4].
• We examined the expression of the DCC gene in 22 tissue samples from human gliomas (glioblastoma multiforme, oligodendroglioma, and mixed oligodendroglioma/astrocytoma) [5].

High impact information on Oligodendroglioma

• The inverse relationship between CDKN2A gene deletions and losses of chromosomes 1p and 19q further implies that these differential clinical behaviors reflect two independent genetic subtypes of anaplastic oligodendroglioma [6].
• OLIG2-positive cells corresponding to neoplastic oligodendrocytes were present in all oligodendrogliomas and oligoastrocytomas [7].
• Cell membranes isolated from brain tissues, obtained surgically from six patients afflicted with drug-resistant temporal lobe epilepsy and from one nonepileptic patient afflicted with a cerebral oligodendroglioma, were injected into frog oocytes [8].
• Here we show that human OLIG genes are expressed strongly in oligodendroglioma, contrasting absent or low expression in astrocytoma [9].
• Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs have been isolated from a human oligodendroglioma cell line [10].

Chemical compound and disease context of Oligodendroglioma

• Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions [11].
• Inefficient removal of O6MeGua in oligodendrogliomas might also account for their response to chemotherapeutic regimens involving alkylating agents such as procarbazine, lomustine, and carmustine [12].
• Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities [13].
• Selective induction by N-nitrosoethylurea of oligodendrogliomas in fetal forebrain transplants [14].
• Human oligodendroglioma cells also demonstrated calcium mobilization in response to receptor activation with U46619 [15].

Biological context of Oligodendroglioma

• To evaluate this possibility, we studied 39 high-grade oligodendrogliomas for homozygous deletions and point mutations of the CDKN2C gene, as well as for allelic loss of 1p [16].
• Survival is significantly better in patients who are younger than 40 years and in patients who have oligodendroglioma or oligo-dominant histology [17].
• Using an integrated genetic and epigenetic analysis of oligodendrogliomas, we show that aberrant CpG island methylation is the most prevalent alteration in these tumors, and the majority of methylated genes are independent of regions affected by deletion [18].
• Coupled with the recent report of rare point mutations of CDKN2C in oligodendrogliomas, these findings suggest that CDKN2C inactivation may be oncogenic in a small percentage of human oligodendrogliomas [16].
• Molecular genetic analysis of von Hippel-Lindau tumor suppressor gene (VHL gene) was performed on 38 tissues of human glial tumors (ependymoma, 1; astrocytoma, 6; oligodendroglioma, 1; oligoastrocytoma, 2; anaplastic oligoastrocytoma, 3; anaplastic astrocytoma, 14; glioblastoma multiforme, 11) [19].

Anatomical context of Oligodendroglioma

• We conclude, therefore, that molecular subtypes of oligodendrogliomas may arise preferentially in certain lobes of the brain and have differential patterns of growth, with tumors having allelic loss of chromosomes 1p and 19q occurring most frequently in the frontal lobes and having a tendency for widespread growth across the midline [20].
• These results indicate that oligodendroglioma cell lines express Types I and II cytokeratin genes [21].
• In the present study, we analyzed human adult brain, fetal spinal cord, and an interleukin-2 (IL-2)-responsive human oligodendroglioma subclone, TC620.6A2, for the presence of mRNAs for the alpha, beta, and gamma chains of the interleukin-2 receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma) [22].
• Bovine cerebrum, including the corpus callosum, and a human oligodendroglioma were investigated by an immunohistochemical technique to determine the distribution of 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) [23].
• We conclude from these data that HO-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression in areas of focal necrosis [24].

Gene context of Oligodendroglioma

• Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas [25].
• In oligodendrogliomas, hypermethylation of RB1 (1 case) and p14ARF (6 cases) were the only detectable genetic changes (7/28, 25%) [25].
• Our data suggest that in classic oligodendrogliomas: 1) 1p/19q tumor status is a powerful predictor of patient survival, even after recurrence; 2) p16 deletions are common progression-associated alterations; and 3) 10q deletions and EGFR amplifications are sufficiently rare to suggest the possibility of alternate diagnoses [26].
• In situ hybridization analyses have revealed that Olig genes are expressed in oligodendroglial lineage cells and are highly expressed in oligodendrogliomas [27].
• Immunohistochemistry and microarray analyses demonstrate higher OLIG2 in anaplastic oligodendrogliomas versus glioblastomas, which are heterogeneous with respect to OLIG2 levels [28].
• The most frequently amplified genes were epidermal growth factor receptor (EGFR) and cyclin-dependent kinase 4/sarcoma amplified sequence (CDK4/SAS) in 17% and 8% of anaplastic oligodendrogliomas, respectively [29].

Analytical, diagnostic and therapeutic context of Oligodendroglioma

• Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy [30].
• From one anaplastic oligodendroglioma (which showed strong IGF-1 immunostaining) the IGF-1 transcripts were characterized after isolation of mRNA followed by amplification using the reverse transcriptase-polymerase chain reaction [31].
• Northern blot analysis, however, revealed increases of EGFR mRNA expression relative to non-neoplastic control brain in 6 of 13 oligodendrogliomas and 10 of 18 anaplastic oligodendrogliomas [32].
• Moreover, a combination of YKL-40 and glial fibrillary acidic protein immunohistochemistry afforded even greater diagnostic accuracy in anaplastic oligodendrogliomas [33].
• Genetic alterations specific for tumor type and tumor progression were investigated in 5 pairs of recurrent astrocytomas and 8 pairs of recurrent oligodendrogliomas by means of interphase in situ hybridization (ISH) to paraffin-embedded, formalin-fixed tissue sections [34].

References