Identification of 2 putative critical segments of 17q gain in neuroblastoma through integrative genomics

摘要: Partial gain of chromosome arm 17q is the most frequent genetic change in neuroblastoma (NB) and constitutes strongest independent factor for adverse prognosis. It assumed that 1 or more genes on contribute to NB pathogenesis by a gene dosage effect. In present study, we applied 17 tiling path BAC arrays panel 69 primary tumors 28 cell lines order reduce current smallest region facilitate identification candidate sensitive genes. all with gain, large distal segments were consistently extra copies no interstitial gains observed. addition these regions breakpoints proximal coordinate 44.3 Mb (17q21.32), smaller (distal 60 at 17q24.1) found superimposed larger minority cases. Positional enrichment analysis overexpressed showed oncogenes are likely located gained immediately breakpoint 2 regions. Interestingly, comparison expression profiles between normal fetal adrenal neuroblasts revealed clusters NB, i.e. 17q21.32 (in cases single gain) 17q24.1, coinciding leading gain.