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<p>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, <i>DAXX</i>/<i>ATRX</i> mutations, activation of the alternative lengthening of telomeres pathway, <i>BEND2</i> 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.</p> Graphical abstract <p></p>

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Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月29日

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  • Michele Bevere,
  • Anastasios Gkountakos,
  • Silvia Valentinuzzi,
  • Simone De Fabritiis,
  • Chee S. Wong,
  • Riccardo De Robertis,
  • Paola Mattiolo,
  • Manuel Gentiluomo,
  • Matteo Fassan,
  • Antonio Pea,
  • Stefano F. Crinò,
  • Michele Simbolo,
  • Andrea Mafficini,
  • Daniele Campa,
  • Sara Cingarlini,
  • Luca Landoni,
  • Rita T. Lawlor,
  • Roberto Salvia,
  • Mirko D’Onofrio,
  • Michele Milella,
  • Volkan Adsay,
  • Lodewijk A. Brosens,
  • Christopher M. Heaphy,
  • Seung-Mo Hong,
  • Aatur D. Singhi,
  • Aldo Scarpa,
  • Claudio Luchini

摘要

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.

Graphical abstract