Characterization of amplicons in neuroblastoma: high-resolution mapping using DNA microarrays, relationship with outcome, and identification of overexpressed genes.

摘要: Somatically acquired chromosomal imbalances are a key feature of neuroblastoma, heterogeneous pediatric solid tumor. Among these alterations, genomic amplification targeting the MYCN oncogene and observed in about 25–30% cases, strongly correlates with advanced stage poor outcome. In this work, we have used BAC SNP arrays as well gene expression to characterize amplifications neuroblastoma. Eighty-eight distinct BACs defining high-level events were identified 65 samples, including 43 tumors 22 cell lines. Although highest recurrence was on chromosome 2, clones chromosomes 8, 12, 16, 17 also revealed several samples. A detailed analysis 2p22-2p25 containing region indicated highly complex patterns number cases. Coamplifications involving other regions explored by FISH three High-resolution then allowed us further refine mapping 25 amplicons 19 either reducing size single continuous amplicon or increasing complexity highlighting multiple noncontiguous amplification. Combined profiling array-CGH data that 12 25% genes targeted actually over-expressed tumor cells, them having already been implicated cancer. Finally, our results suggest presence localized outside addition amplification, may be linked particularly severe outcome neuroblastoma patients. © 2008 Wiley-Liss, Inc.