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

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. Overall design: 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.