ATRX and metastatic neoplasm: Interestingly, previous studies revealed that patients with metastatic disease and ALT showed longer survival, while the opposite was true for non-metastatic tumors, suggesting a possible dual role in later PanNET progression [12, 51].While its association with DAXX/ATRX loss of function was already established previously, to our knowledge this is the first report correlating hypomethylation of telomeric and pericentromeric regions with ALT activation and CNA in PanNETs [48, 50], thus revealing possible driving mechanisms.