Abstract
Comparative genomic hybridization (CGH) was applied to 35 neuroblastomas to obtain a global view of genetic imbalances. Results were validated by means of Southern blot hybridization (detection of N-myc amplification), loss of heterozygosity (LOH) studies (detection of deletion 1p), and interphase cytogenetics [dual labelling fluorescence in situ hybridization (FISH) of centromeric 17 and erbB-2]. CGH allowed sensitive detection of N-myc amplification and chromosome 1p deletion, representing the most established prognostic markers of neuroblastoma. In addition, a high rate of chromosome 17 aberrations (63 per cent) with possible prognostic relevance was observed. Previously unreported high level copy number increases indicating oncogene amplification were mapped to chromosome subbands 2p13-14 and 3q24-26. Other recurrent regional chromosomal aberrations were localized on 11q, 12q, 13q, 14q, and 15q. CGH results were fully consistent with data of Southern blot analysis and LOH study, as well as interphase cytogenetics. These results show that CGH is a sensitive method for the detection of all prognostically relevant genetic alterations in neuroblastomas; that CGH considerably simplifies the detection of these alterations, resulting in a single methodological approach; and that CGH is a powerful tool to elucidate previously unknown genetic changes in neuroblastomas.
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