PTEN alterations of the stromal cells characterise an aggressive subpopulation of pancreatic cancer with enhanced metastatic potential

•We assessed the mechanisms for phosphatase and tensin homolog (PTEN)-loss in pancreatic ductal adenocarcinoma (PDAC).•PTEN-deletion is a major cause of PTEN-loss in PDAC and correlates with aggressive features and worse outcome.•PTEN-loss in both tumour and juxta-tumoural stroma characterizes a PDAC subgroup with enhanced metastatic potential.•PTEN-loss in juxta-tumoural stroma is mostly due to PTEN haplo-insufficiency.•PTEN silencing by miR-21 acts cooperatively but also independently of the genetic factors to enhance PTEN-loss.