DNA methylation patterns facilitate tracing the origin of neuroendocrine neoplasms

Neuroendocrine neoplasms (NEN) are thought to originate from diffuse endocrine networks and therefore most frequently occur in the gastrointestinal tract and lungs. The liver is a frequent site of metastasis of NEN but also the presence of primary hepatic NEN has been proposed. Due to the impact on disease management, it is urgently required to discriminate the origin of hepatic NEN metastases and to identify clinically relevant subgroups. Using a comprehensive set of NEN (N=198), we showed that the DNA methylation profile of NEN of distinct anatomical localizations differed significantly and primary tumor-metastasis pairs clustered together, enabling us to identify the tumor origin.