A common and histologically well defined subtype of glioma are the oligodendroglial brain tumors. Oligodendrogliomas differ from the other glioma subtypes in clinical behavior with respect to overall prognosis and a relatively better and longer lived response to chemotherapy and radiotherapy. Oligodendrogliomas have clearly distinct gene expression profiles and are also cytogenetically distinct: approximately 70% of all oligodendrogliomas have a combined loss of the entire short arm of chromosome 1 and loss of the entire long arm of chromosome 19 . Loss of these hapten scfv ribosome chromosomal arms in oligodendrogliomas is highly correlated with chemosensitivity; approximately 80�C90% of oligodendroglial tumors with LOH on 1p and 19q respond to chemotherapy. Conversely only 25�C 30% of tumors that have retained the short arm of chromosome 1p are sensitive to chemotherapy. In summary, oligdendrogliomas are a clinically, histologically, cytogenetically and molecularly distinct and well defined subgroup of glioma. In spite of these clearly distinct clinical, histological and molecular features, little is known on the genetic changes that drive these tumors. Thusfar, IDH1/IDH2 and, to a much lesser extent, TP53 and PIK3CA are the only genes that are mutated at significant frequency in this tumor type. The remarkably high frequency of LOH of 1p and 19q suggests the remaining arms harbor yet to be identified tumor suppressor genes. Identification of the causal genetic changes is important because they form direct targets for treatment: Tumor growth depends on these acquiredsomaticchanges both in oncogenes and in tumor suppressor genes. In this study we therefore aimed to identify genetic changes in all exons, microRNAs, splice sites and promoter regions on 1p or 19q using array capture and Next Generation Sequencing. Experiments were performed on 7 oligodendrogliomas and 4 had matched control DNA samples. Of the 514 candidate variants 77% were not confirmed on tumor DNA using direct sequencing. Such variants likely represent amplification artefacts and/or sequencing artefacts. A further 21% could be confirmed in the tumor samples, but the variant was also present in the matched control DNA. These variants may represent selective allele amplification and sequencing. In summary, of the 514 candidates subject to direct sequencing, one variant was validated. This variant is a missense mutation and affects the last amino acid of ARHGEF16 in sample 8. It should be noted that the absence of trace wt sequence in the chromatogram confirms the high tumor percentage in this sample. The base is highly conserved. However, it remains to be determined whether the identified mutation affects its RhoA guanine exchange function and oncogenic transformation potential. None of the other 6 samples contained changes in the coding sequence of ARHGEF16. In addition, we failed to identify mutations in the last exon of ARHGEF16 in an additional 32 samples from the same molecular cluster using direct sequencing. No small homozygous deletions were identified on SNP 6.0 and 250 k Nsp arrays from 23 oligodendrogliomas. We have systematically sequenced all exons, miRNAs, splice sites and promoter regions on 1p and 19q. Of the 514 candidate variants in coding exons, miRNAs, splice sites and promoter regions, only one was validated: a missense mutation in ARHGEF16 affecting the PDZ-binding domain. ARHGEF16 lies on 1p36 a region that is commonly deleted in gliomas. However, no other genetic changes were detected in the ARHGEF16 gene in a panel of 32 additional oligodendrogliomas, though the promoter is frequently hypermethylated.