Abstract
Neuroblastoma (NB) is a pediatric tumor characterized by high genetic heterogeneity. Although the prognostic significance of some genomic abnormalities (i.e., MYCN amplification, 1p loss, and 17q gain) is recognized, genes that are involved in chromosome rearrangements remain largely unknown. Considerable progress has been made over the last years in characterizing DNA abnormalities by metaphase comparative genomic hybridization (mCGH) and array CGH (aCGH). Here we report a pilot study of 5 localized and 12 disseminated NB by 44,000 and of 4 out of 17 cases by 244,000 oligonucleotide aCGH. Localized tumors were predominantly characterized by losses of whole chromosomes 3, 4, 10, and 16, and gains of 6, 7, 8, 13, 17, 18, and 20, whereas disseminated tumors showed several structural aberrations including 17q gain and 3p and 11q losses. Characterization of chromosome 2p in MYCN-amplified NB revealed several structural rearrangements with regions of gain interspersed among sites of amplification, indicating that the MYCN amplicon may encompass several genes. The high-resolution zooming in chromosomal aberrant regions detected several micro-deletions and micro-amplifications in the NB genome. Our results indicate that the increased sensitivity of the aCGH also allows the identification of DNA aberrations in challenging samples (i.e., NB showing tissue and genetic heterogeneity).
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