LTHOUGH genetic study methods have dramatically progressed during the last 20 years, histological classification of glial neoplasms is still based on the morphological similarities between tumor cells and non- neoplastic cells. 8 Accurate classification is of the utmost im- portance, however, because the response of gliomas to ther- apy shows a correlation with cell lineage. 3,8,13 Diffuse astrocytomas, such as glioblastomas (the most frequent and malignant variant), and oligodendrogliomas are defined as being composed of astrocytes and oligoden- drocytes that may derive from the neoplastic transformation of mature glial cells. The strong glial fibrillary acidic pro- tein expression in astrocytomas is compatible with that hy- pothesis; however, markers of mature oligodendrocytes are not found in oligodendrogliomas. An alternative hypothesis is that gliomas may arise from dividing progenitor cells. In vitro O-2A rat progenitor cells differentiate into oligodendrocytes in serum-free medium and into Type II astrocytes in serum-containing medium. 19 The O-2A progenitor cells expressed some antigenic epi- topes such as the PDGFR, 4,14 the NG2 chondroitin sulfate proteoglycan, and the PEN5 epitope in a temporally regu- lated sequence. 5,17 Data from two recent studies have shown that some gliomas, especially oligodendrogliomas and pi- locytic astrocytomas (a variant of circumscribed gliomas), expressed these markers, thus providing evidence that glial tumors may arise from oligodendrocyte O-2A progenitor cells. 5,17 Other interesting markers are the transcriptional factors of the bHLH family. The bHLH proteins play a key role in J Neurosurg 99:344–350, 2003 344 Shared oligodendrocyte lineage gene expression in gliomas and oligodendrocyte progenitor cells CORINNE BOUVIER, M.D., CATHERINE BARTOLI, PH.D., LUCINDA AGUIRRE-CRUZ, M.D., ISABELLE VIRARD, CAROLE COLIN, CARLA FERNANDEZ, JOANY GOUVERNET , M.D., AND DOMINIQUE FIGARELLA-BRANGER, M.D., PH.D. Laboratoire des Interactions Neurone-Glie, Groupe Hospitalier Pitié-Salpétrière, Paris; Laboratoire de Biopathologie Nerveuse et Musculaire, Faculté de Médecine; NMDA-Centre National de la Recherche Scientifique UMR 6156, Institut de Biologie et du Développement, Parc Scientifique de Luminy; and Service de l’Information Médicale, Hôpital de la Timone, Marseille, France Object. Gliomas (astrocytic and oligodendroglial) are the most frequently occurring primary neoplasms in the central nervous system (CNS). Histological classification, which can be performed to distinguish astrocytomas from oligoden- drogliomas, is essentially based on pathological features and has great prognostic and therapeutic value but lacks repro- ducibility. Specific markers of cell lineage, especially those for oligodendrogliomas, are still lacking. The oligodendrocyte lineage (OLIG) genes, transcriptional factors of the basic helix-loop-helix family, have been recently identified in oligo- dendrocyte progenitor cells (OPCs) in the CNS of developing and adult rodents. Data from a few studies have shown in a small series of brain tumors that OLIG genes characterize oligodendrogliomas. To search for a differential expression of the OLIG genes in subgroups of brain tumors, the authors investigated OLIG1 and OLIG2 gene expression. Methods. Using semiquantitative reverse transcription–polymerase chain reaction (RT-PCR), the authors analyzed a se- ries of 89 tumors (71 astrocytic and oligodendroglial tumors, eight ependymomas, three medulloblastomas, four meningi- omas, and three schwannomas) and normal human brain tissue samples. It was demonstrated that OLIG gene expression was largely limited to glial tumors, that is, astrocytomas and oligodendrogliomas. A very low level was detected in ependy- momas, whereas other tumors lacked OLIG gene expression altogether. Surprisingly, OLIG1 and OLIG2 expression was not limited to oligodendroglial tumors, but was observed in astrocytic lesions as well, independent of tumor grade. Inter- estingly, these genes were expressed at the highest level in pilocytic astrocytomas according to semiquantitative RT-PCR results, which were confirmed on dot blot analysis. In situ hybridization showed that the OLIG2 gene was expressed by tumor cells in pilocytic astrocytomas as well as those in oligodendrogliomas. Conclusions. The OLIG genes are additional markers shared by all gliomas and OPCs. These markers may help to clas- sify gliomas, to improve understanding of their histogenesis, and to identify new therapeutic targets. KEY WORDS • glioma • oligodendroglioma • oligodendrocyte lineage gene • oligodendrocyte progenitor cell • pilocytic astrocytoma A J. Neurosurg. / Volume 99 / August, 2003 Abbreviations used in this paper: bHLH = basic helix-loop-helix; cDNA = complementary DNA; CNS = central nervous system; cRNA = complementary RNA; EDTA = ethylenediamine tetraace- tic acid; GAPDH = glyceraldehyde-3-phosphate-dehydrogenase; mRNA = messenger RNA; OLIG = oligodendrocyte lineage; OPC = oligodendrocyte progenitor cell; PDGFR = platelet-derived growth factor receptor–; RT = reverse transcription; RT-PCR = RT–poly- merase chain reaction.