Sex-specific transcriptional differences and loss of gene imprinting in pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PNETs) occur more frequently in men and are associated with higher mortality in males; however, the molecular basis for these sexual dimorphisms is unclear. Here, we demonstrate that PNETs are associated with the emergence of unique sex-specific transcriptomic differences that are not observed in non-neoplastic pancreatic islet tissues. We also show that while widespread sex-specific differences are present in the DNA methylation landscapes of control pancreatic islets, they are erased in PNETs. This includes a loss of imprinting with regards to many genes. These results implicate an emergence of sex-associated genetic and epigenetic dysregulations in PNETs.