Chromosomal imbalances detected by array comparative genomic hybridization in human oligodendrogliomas and mixed oligoastrocytomas
Nucleic Acid Hybridization
Loss of heterozygosity and fluorescence in situ hybridization (FISH) studies have shown that deletions of 1p and 19q are highly prevalent in oligodendroglioma. However, these tumors have not been comprehensively screened for other alterations in chromosomal dosage. In this study, we used array-based comparative genomic hybridization (CGHa) of mapped BAC DNA to screen for such alterations in 31 oligodendrogliomas (20 grade II, 9 grade III, and 2 grade IV) and 4 mixed oligoastrocytomas (1 grade I, 1 grade II, and 2 grade IV). The most frequent aberrations were loss of 1p (17 cases; 49%) and 19q (15 cases; 43%) and combined loss of 1p/19q (13 cases; 37%). In addition, deletion of 4q, 5p, 9p, 10q, 11p, and 13q was observed in 10, 4, 8, 4, 4, and 13 cases, respectively; loss of whole chromosomes 4, 9, and 13 in 4, 1, and 7 cases, respectively; gain of 7p, 8q, 10p, and 11q in 6, 6, 5, and 10 cases, respectively, and gain of whole chromosomes 7 and 11 in 2 patients each. Minimally altered regions detected by CGHa involved chromosome bands 1p36.32, 4q33, 5p15, 8q24, 11p15, and 19q13.3. Univariate analysis of all 35 cases suggested that combined deletion of 1p and 19q is associated with better survival (P = 0.03). In addition, 8q gain in the oligodendrogliomas was strongly associated with poor outcome (P = 0.002). Also associated with poor disease outcome were alterations that had low prevalence in the pure oligodendrogliomas, including loss of 3q, 9q, and 12q and gain of 1p, 8p, and 10q. In summary, in oligodendrogliomas, CGHa was able to detect novel small alterations in chromosomal dosage that had not been previously detected by other methods. In addition, our findings support the hypotheses that oligodendroglioma can be classified into several groups by CGHa analysis and that specific alterations in genetic dosage may have biologic or clinical significance.