Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

Abstract

Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management.

Differences between Well-Differentiated Neuroendocrine Tumors and Ductal Adenocarcinomas of the Pancreas Assessed by Multi-Omics Profiling

“…As reported previously, recurrent mutations of MEN1 and VHL are identified in distinct NET hereditary syndromes, and those involving DAXX, ATRX (found in a mutually-exclusive manner in pNETs) [30], and mTOR pathway genes (PTEN, TSC2, NF1, PIK3CA) are commonly found in sporadic PNETs [21,31,32]. In turn, in most sporadic and familial PDACs, four key driver mutations in KRAS, TP53, SMAD4, and CDKN2A, and mutations in other oncogenes (c-myc, PAK4, HER2), tumor suppressor genes (PTEN, BRCA2, PALB2, and PRSS1), and DNA mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) have been found [9].…”

Operationsindikationen bei Tumoren der Bauchspeicheldrüse

“…Sporadische pNEN werden in funktionell aktive (f-pNEN) und funktionell nicht aktive (nf-pNEN) Tumoren eingeteilt, wobei nf-pNEN häufiger vorkommen [28,29]. nf-pNEN werden nochmals anhand einer virtuellen Grenze bei einer Größe von 2 cm differenziert.…”