Focal DNA Copy Number Changes in Neuroblastoma Target MYCN Regulated Genes

• DOI: 10.1371/journal.pone.0052321
• Publication Date: 2013-01-04T22:10:18Z
• Authors: Candy Kumps; Annelies Fieuw; Pieter Mestdagh; Björn Menten; Steve Lefever; Filip Pattyn; Sara De Brouwer; Tom Sante; Johannes Hubertus...; Alexander Schramm; Nadine Van Roy; Tom Van Maerken; Rosa Noguera; Valérie Combaret; Christine Devalck; Frank Westermann; Geneviève Laureys; Angelika Eggert; Jo Vandesompele; Katleen De Preter; Frank Speleman
• Keywords: Gene dosage; N-Myc

Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system cells. Recurrent genomic alterations include MYCN and ALK amplification as well recurrent patterns of gains losses whole or large partial chromosome segments. A recent genome sequencing effort yielded no frequently recurring mutations in genes other than those affecting ALK. However, the study further stresses importance DNA copy number this disease, particular for implicated neuritogenesis. Here we provide additional evidence focal losses, which are predominantly observed amplified tumors. 5 kb gain encompassing regulated miR-17~92 cluster sole gene was detected a neuroblastoma cell line analyses array CGH data set demonstrated enrichment target amplifications. Next applied integrated genomics analysis to prioritize down mediated by driven miRNAs within regions heterozygous homozygous deletion. We identified RGS5, negative regulator G-protein signaling vascular normalization, invasion metastasis, targeted deletion, new gene, through activated miRNAs. In addition, expand regulatory network controlling TGFß with ring finger protein 11 encoding RNF11, previously shown be member miR-19b. Taken together, our indicate that imbalances (1) signaling, possibly selected reinforce oncogene addiction (2) serve resource identifying molecular targets treatment.