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. 2017 May 1;36(35):5075–5082. doi: 10.1038/onc.2017.128

Figure 4.

Figure 4

Mouse NCC-derived NBL recapitulates human NBL gene signatures and chromosomal changes. (a) ENRICHR analysis comparing top expressed genes from NCC-derived NBL to gene signatures of 917 cell lines in the Cancer Cell Line Encyclopedia (CCLE). Data is presented as average rank score (-Log10(pValue) for each cancer subtype. The number of cell lines represented in each cancer subtype is shown in parentheses and error is standard deviation. (b) The NCC-derived NBL gene signature in comparison to each of the individual NBL cell lines in the CCLE preferentially matches N-Myc amplified NBL (blue) than N-Myc wild type NBL (red). (c) Dot-blot comparing the log ratio of N-Myc amplified NBL (GEO data set: GSE32664) to human adrenal (GEO data set: GSE39716) versus the log ratio of N-Myc NCC-derived NBL (Affymetrix Mouse 2.0 ST arrays (ThermoFisher Scientific), GEO data set: GSE94914) versus mouse adrenal (GEO data set: GSE21829). (d) Genes differentially expressed between N-Myc NCC-derived NBL (Affymetrix Mouse 2.0 ST arrays, ThermoFisher Scientific: GSE94914) and mouse adrenal (GEO data set: GSE21829) share molecular signatures as determined by gene set enrichment analysis with gene sets downstream of CCND1 and CDK4 in primary NBLs (Molenaar) and cancer-specific genes shared between primary pediatric tumors and pediatric xenografts (Whiteford). (e) Average NCC-derived NBL tumor to normal liver genomic DNA ratio following array comparative genomic hybridization (aCGH). A log2ratio threshold of 0.3 was used to identify amplifications and −0.4 to identify deletions. NCC-derived tumors show amplification of the region syntenic to human Chromosome 17q23-qter on mouse chromosome 11. (f) NCC tumors have deletions in mouse chromosome 4 in the region syntenic to human 1p36. (g) NCC tumors have amplification of the region syntenic to human 2p13-15 on mouse chromosome 11. The positions of a subset of proposed NBL oncogenes and tumor suppressors from each region are indicated.