Disease relevance of OLIG2

• Immunohistochemical analyses demonstrated that the mean immunopositive proportion of OLIG2 was 82% in anaplastic oligodendrogliomas but only 34% in anaplastic astrocytomas [1].
• The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas [2].
• Immunohistochemistry and microarray analyses demonstrate higher OLIG2 in anaplastic oligodendrogliomas versus glioblastomas, which are heterogeneous with respect to OLIG2 levels [2].
• OLIG2 protein expression is present but inconsistent and generally lower in most other brain tumors and is absent in non-neuroectodermal tumors [2].
• We investigated the expression of OLIG2 by in-situ hybridisation in 21 brain tumours: nine grade II and III oligodendrogliomas, three grade II oligoastrocytomas, and nine non-oligodendroglial tumours (four grade IV astrocytomas, two meningiomas, a dysembryoplastic neuroepithelial tumour, and two metastases) [3].

Psychiatry related information on OLIG2

• It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone [4].
• Finally, the formation of oligodendrocytes is triggered by an increase in the activity of bHLH factors Olig1 and Olig2 that may be coupled with a decrease in Id activity [5].

High impact information on OLIG2

• By temporally selective interactions with other transcription factors, Olig2 first directs motor neuron fate and later switches to promoting oligodendrocyte production [6].
• The bHLH repressor Olig2 participates in the transcriptional code governing cell fate specification in the ventral spinal cord [6].
• At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2 [7].
• Functional analysis of PDGF signaling in these neural progenitors resonates in provocative ways with an older body of literature on PDGF autocrine loops in malignant glioma and with more recent observations on the bHLH transcription factor Olig2 [8].
• OLIG2-positive cells corresponding to neoplastic oligodendrocytes were present in all oligodendrogliomas and oligoastrocytomas [3].

Biological context of OLIG2

• Analysis of mice lacking Olig function demonstrates a failure of NG2 cell development at embryonic and perinatal stages that can be rescued by addition of a transgene containing the human OLIG2 locus [9].
• To search for a differential expression of the OLIG genes in subgroups of brain tumors, the authors investigated OLIG1 and OLIG2 gene expression [10].
• RESULTS: The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; P<.001), rs1059004 (minor allele frequency, 44%; P = .005), and rs9653711 (minor allele frequency, 44%; P = .004) [4].
• Analysis of OLIG2 in a case-control sample (n = approximately 1,400) in the U.K. revealed several SNPs to be associated with schizophrenia (minimum P = 0.0001, gene-wide P = 0.0009) [11].
• These results indicate that OLIG2 suppresses the proliferation of U12-1 and that this effect is mediated by transactivation of the p27(Kip1) gene, and low expression of OLIG2 may be related to the malignant behavior of human glioblastoma [12].

Anatomical context of OLIG2

• Further, exposure of cultured progenitor cells to BMP4 changed the intracellular localization of OLIG1 and OLIG2 from a predominantly nuclear to a predominantly cytoplasmic localization [13].
• OLIG2 protein is faithfully restricted to normal oligodendroglia and their progenitors in human brain [2].
• Although expression of OLIG2 is normally restricted to neural tissues, overexpression of OLIG2 has been shown in patients with precursor T-cell lymphoblastic lymphoma/leukemia (pre-T LBL) [14].
• In the current study, we found that overexpression of OLIG2 was not only found in oligodendroglioma samples and normal neural tissue but also in a wide spectrum of malignant cell lines including leukemia, non-small cell lung carcinoma, melanoma, and breast cancer cell lines [14].
• Ectopic OLIG2 expression in the thymus was only weakly oncogenic as only 2 of 85 mice developed pre-T LBL [14].

Associations of OLIG2 with chemical compounds

• Interestingly, a subset of the bromodeoxyuridine-positive cells expressed olig2 in the embryonic retina [15].

Regulatory relationships of OLIG2

• Expression of BHLHB1 dramatically inhibited E2A-mediated transcription activation in NIH 3T3 fibroblasts and Jurkat T cells [16].
• The OLIG2 gene is also highly expressed in brain regions implicated in OCD [4].
• A novel function of OLIG2 to suppress human glial tumor cell growth via p27Kip1 transactivation [12].

Other interactions of OLIG2

• However, almost 60% of transgenic mice that overexpressed both OLIG2 and LMO1 developed pre-T LBL with large thymic tumor masses [14].
• We identified a previously unreported transcript, designated BHLHB1 (for basic domain, helix-loop-helix protein, class B, 1) that had been activated by the translocation [16].
• We found prominent coexpression of GFAP and OLIG2 in gliofibrillary and minigemistocytic oligodendrocytes [17].
• These findings suggest that CNP and OLIG2 are unlikely to be related to the development of schizophrenia in the Japanese population [18].
• In clear cell primary brain tumours lacking OLIG2 expression, differential diagnosis may require additional immunohistochemical markers [17].

Analytical, diagnostic and therapeutic context of OLIG2

• In conclusion, combining Olig mRNA expression and immunohistochemistry of OLIG2 enables oligodendrogliomas to be distinguished from glioblastomas and other astrocytic glial tumors [1].
• Recent in situ hybridization studies showed that mRNA levels of OLIG1 and OLIG2 transcription factors are elevated in oligodendrogliomas [19].
• To clarify whether OLIG is a tumor-specific marker for oligodendrogliomas, we have investigated the expression of Olig transcripts by semiquantitative RT-PCR assay and OLIG2 protein with a new antibody in a variety of glial tumors [1].
• High OLIG expression alone has been proposed to distinguish oligodendrogliomas from astrocytomas, so we critically evaluated OLIG2 as a marker by immunohistochemical and oligonucleotide microarray analysis [2].
• Electrophoretic mobility shift assays confirmed that a nuclear extract of OLIG2-expressing U12-1 cells contained a protein complex that binds to the CTF site of the p27(Kip1) gene promoter [12].

References