Loss of heterozygosity (LOH) on chromosomal arms 1p and 19q is the most common genetic alteration in oligodendroglial tumors and associated with response to radio-and chemotherapy as well as favorable prognosis. Using microsatellite analysis, we previously identified the chromosomal regions 1p36. 22-p36.31 and 19q13.3, as candidate tumor suppressor gene regions being commonly deleted in these tumors. To identify genes within these regions that are downregulated in oligodendroglial tumors with LOH 1p/19q, we performed cDNA microarray-based RNA expression profiling of 35 gliomas with known allelic status on 1p and 19q, including 7 oligodendrogliomas and 8 diffuse astrocytomas of World Health Organization (WHO) grade II, as well as 14 anaplastic oligodendrogliomas and 6 anaplastic oligoastrocytomas of WHO grade III. The microarrays used for expression profiling carried 7,000 gene-specific cDNAs, with complete coverage of the genes located in 1p36. 13-p36.31 and 19q13.2-q13.33. Microarray analysis identified 8 genes from these regions (MGC4399, SRM, ICMT, RPL18, FTL, ZIN, FLJ10781 and DBP), which all showed significantly lower expression in 1p/19q-deleted gliomas when compared to gliomas without 1p/19q losses. Quantitative real-time reverse transcription-PCR analyses were performed for the MGC4399, ICMT and RPL18 genes and confirmed the microarray findings. In addition, we found that the cytosolic phospholipase A2 (PLA2G4C) gene at 19q13.3 demonstrated significantly lower expression in anaplastic oligodendrogliomas (WHO grade III) when compared to well-differentiated oligodendrogliomas (WHO grade II). Taken together, our study provides a set of interesting novel candidate genes that may play important roles in the pathogenesis of oligodendroglial tumors. ' 2006 Wiley-Liss, Inc.Key words: gene expression profiling; loss of heterozygosity; DNA microarray; oligodendroglioma; tumor suppressor gene Gliomas are the most common primary brain tumors and constitute a heterogeneous group of neoplasms with respect to morphological appearance, biological behavior, genetic alterations, as well as response to therapy and clinical outcome. Astrocytic tumors are the most common gliomas, with glioblastoma multiforme being the most malignant and, at the same time, most frequent astrocytic tumor. In contrast, oligodendroglial tumors, comprising oligodendrogliomas and mixed oligoastrocytomas, are estimated to account for only 5-18% of all gliomas.1 Molecular genetic studies have revealed that the development of astrocytic and oligodendroglial gliomas is caused by distinct genetic alterations, which may be important for the refinement of glioma classification based on genomic profiling.2 The genetic hallmark of oligodendroglial tumors is the combined loss of heterozygosity (LOH) on chromosomal arms 1p and 19q (LOH 1p/19q), which is rare in astrocytic tumors but found in up to 80% of oligodendrogliomas and 50% of oligoastrocytomas.3 Importantly, LOH 1p/19q has emerged as an independent predictive marker of better response to radio-and ...