Transcriptome profiling of caspase-2 deficient lymphomas from EµMyc and neuroblastomas from Th-MycN mice

The project used next generation sequencing for RNA-seq analysis, to identify transcriptome changes associated with tumorigenesis in two different caspase-2 knockout mice models. We describe key changes in both lymphoma and neuroblastoma associated genes in the two tumor types that may contribute to tumor outcome following loss of Casp2. We identified a panel of genes with altered expression in Th-MYCN/Casp2-/- tumors, that are strongly associated with neuroblastoma outcome, and which have roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In addition, we found that key changes in gene expression in the EµMyc/Casp2-/- tumors, are associated with increased immune signaling and suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues. Overall design: We used tumors from EµMyc/Casp2-/- mice (which are more aggressive compared to their EµMyc counterarts) as well as tumors from Th-MycN/Casp2-/- mice (which show delayed tumour onset compared to Th-MycN mice) and compared the transcriptomes to their Casp2 wild type counterpart tumors. Sequencing was carried out with Illumina HiSeq 2000 and used short, single-end reads (1x 50bp flow cells) with 4 samples per lane. This yielded approximately 20-30 million raw reads per sample.

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Dorstyn L, Hackett-Jones E, Nikolic A, Norris MD, Lim Y, Toubia J, Haber M, Kumar S