Very little is known of the genes and mechanisms contributing to the genesis of oligodendrogliomas, a subtype of primary brain tumors. 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. In contrast, a subset of the gene-associated CpG islands are preferentially affected by converging methylation and deletion, including a putative zinc finger gene, ZNF342, located in a commonly deleted region at chromosome 19q13. ZNF342 expression is specifically decreased in primary oligodendrogliomas and up-regulated in glioma cell lines treated with a demethylating agent, whereas the expression level of the adjacent gene, Gemin7, is not consistently altered in these samples. This initial integrated approach identifies novel targets of gene silencing, and provides a more comprehensive view of the genes and mechanisms underlying oligodendrogliomas.