A cross species and multi-omics (including metabolomics) analysis in pancreatic neuroendocrine tumours

Pancreatic neuroendocrine tumor (PanNET) is relatively infrequent but is nevertheless metastatic. Seeking to extend a new paradigm of personalized medicine, we performed an integrative analysis of transcriptomic (mRNA and microRNA) and mutational profiles and defined three clinically relevant human PanNET subtypes. Importantly, cross-species analysis revealed two of these three subtypes in a well-characterized, genetically engineered mouse model (RIP1-Tag2) of PanNET and its cell lines. Each subtype share similarities to distinct cell types in pancreatic neuroendocrine development, features are reflected in their metabolic profiles. Subtype-specific molecular signatures metabolites are proposed to identify these subtypes. RNA was extracted from fresh frozen archival patient PanNET samples and hybridized on Affymetrix GeneChip human Gene 1.0 ST arrays. The CEL files were processed using R based bioconductor and normalized values were obtained using RMA.