Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape
Pancreatic neuroendocrine neoplasms (PanNENs) constitute a heterogeneous group of tumors distinguished by substantial variability in morphology, immunophenotype, molecular characteristics, and clinical behavior. In recent years, the advent of multiple omics-based methodologies has significantly enhanced our understanding of these neoplasms. Integrating histology and genomics with survival analyses has clarified that the fundamental distinction within this disease spectrum lies between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Furthermore, genomics, transcriptomics, and epigenetic profiling have deepened the granularity of the PanNET landscape, revealing marked differences even within the same diagnostic category, with important clinical implications. For example, DAXX/ATRX mutations, activation of the alternative lengthening of telomeres pathway, BEND2 gene fusions, and an α-cell transcriptional profile are more frequently associated with adverse outcomes. Additional omics approaches, including metabolomics, proteomics, radiomics, and the more recently developed spatially resolved methodologies, are further expanding current knowledge in this challenging field. In this review, we provide an integrated overview of PanNENs, synthesizing insights generated across diverse multi-omics platforms.
Authors
- Michele Simbolo (ORCID: https://orcid.org/0000-0002-0866-4499)
- Antonio Pea (ORCID: https://orcid.org/0000-0002-0509-6756)
- Sara Cingarlini (ORCID: https://orcid.org/0000-0003-4786-4781)
- Manuel Gentiluomo (ORCID: https://orcid.org/0000-0002-0366-9653)
- Αναστάσιος Γκουντάκος (ORCID: https://orcid.org/0000-0001-9001-0293)
- Paola Mattiolo (ORCID: https://orcid.org/0000-0002-5601-0879)
- Simone De Fabritiis (ORCID: https://orcid.org/0000-0001-6404-6962)
- Silvia Valentinuzzi (ORCID: https://orcid.org/0000-0002-1561-3542)
- Matteo Fassan (ORCID: https://orcid.org/0000-0001-6515-5482)
- Christopher M. Heaphy (ORCID: https://orcid.org/0000-0003-4264-1810)
- Luca Landoni (ORCID: https://orcid.org/0000-0002-2474-3496)
- Lodewijk A Brosens
- Riccardo De Robertis
- Rita T. Lawlor
- Aatur D. Singhi (ORCID: https://orcid.org/0000-0003-3930-7096)
- Daniele Campa
- Seung-Mo Hong
- Mirko D’Onofrio
- Michele Milella
- Chee S. Wong
- Stefano F. Crinò
- Roberto Salvia
- Aldo Scarpa
- Michele Bevere
- Claudio Luchini
- Andrea Mafficini
- Volkan Adsay
Institutions
- University of Pisa (IT)
- Ulsan College (KR)
- University of Verona (IT)
- Boston Medical Center (US)
- Koç University (TR)
- University of Padua (IT)
- Democritus University of Thrace (GR)
- Utrecht University (NL)
- Asan Medical Center (KR)
- University Medical Center Utrecht (NL)
- University of Chieti-Pescara (IT)
- University of Ulsan (KR)
- Istituto Oncologico Veneto (IT)
- University of Pittsburgh Medical Center (US)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Queen Elizabeth University Hospital (GB)
- Pancreas Centre (Canada) (CA)
- University of Birmingham (GB)
Publication Details
- Journal
- Molecular Cancer
- Published
- 2026-05-29
- DOI
- https://doi.org/10.1186/s12943-026-02697-4
- Primary Topic
- Neuroendocrine Tumor Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fondazione AIRC per la ricerca sul cancro ETS
- Fondazione Italiana per la ricerca sulle Malattie del Pancreas
- Fondazione Cassa di Risparmio di Verona Vicenza Belluno e Ancona