Characterization of the 1p/19q Chromosomal Loss in Oligodendrogliomas Using Comparative Genomic Hybridization Arrays (CGHa)

Loss of genetic material from the short arm of chromosome 1 and the long arm of chromosome 19 in anaplastic oligodendrogliomas has been shown to predict responsiveness to chemotherapy. Currently, the most common approach used to detect this loss of 1p/19q material employs microsatellite/FISH analysis using markers along the length of these chromosome arms. This analysis is highly focused and carried out on a locus-by-locus basis and gives no indication of the extent of other genetic changes occurring in the tumor cells, which may be important in future studies to explore genetic heterogeneity in the response to treatment. We have investigated the use of comparative genomic hybridization arrays (CGHa) of bacterial artificial chromosomes (BACs) in the identification of tumor samples that carry loss of the 1p/19q chromosome arms. These BAC arrays carry approximately 6,000 BAC clones and provide an average inter-BAC resolution of 500 Kb. Using this approach we have clearly shown that 1p/19q loss in these cases, when compared with microsatellite-mediated detection of loss of heterozygosity, is due to physical hemizygous deletion of the whole chromosome arms in all cases. Furthermore, CGHa allows the simultaneous definition of the other genetic changes that are occurring in the tumors. From our survey of 14 tumors consisting of low-grade oligodendrogliomas (n = 6), anaplastic oligodendrogliomas (n = 5), or mixed oligoastrocytoma (n = 3), we were able to demonstrate the presence of additional genetic markers that were characteristic of the various grades of tumors as well as novel changes that had occurred. Thus, CGHa provides a robust, high throughput, genome-wide analysis of genetic changes of oligodendroglial tumors that can be used not only to predict chemo-responsiveness but also place these genetic changes in the context of other abnormalities in the same experiment without the need for extensive chromosome or LOH analysis.