Cell state programs offer a potential axis for classifying neuroendocrine tumors.
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) arise from hormone-producing cells in the gut and pancreas. Despite increasing incidence of these tumors, therapeutic options remain limited. Well-differentiated GEP-NETs are classified by anatomic site, morphology, and proliferation indices, but this approach offers limited prognostic resolution among phenotypically similar tumors and constrains personalization of treatment decisions. In this issue of the JCI, Karam, Hoffman, and colleagues profiled 38 pancreatic and small-intestinal NETs using joint single-nucleus RNA and ATAC sequencing and projected the resulting malignant cell-associated programs onto matched spatial transcriptomes. Two conserved malignant states emerged: neuronal-like and secretory neuroendocrine. These states span a continuum in both organ sites, are enriched for largely different transcription factor motifs, and occupy distinct microenvironmental niches. Secretory program scores trended higher in metastatic disease and may carry prognostic value. Taken together, these data describe NET heterogeneity as a cell state axis linked to tissue architecture.
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BibTeX
@article{dulai2026cell,
title = {{Cell state programs offer a potential axis for classifying neuroendocrine tumors.}},
author = {Parambir S Dulai},
journal = {The Journal of clinical investigation},
year = {2026},
month = nov,
doi = {10.1172/jci213026},
url = {https://europepmc.org/article/MED/42969226},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cell state programs offer a potential axis for classifying neuroendocrine tumors.
AU - Parambir S Dulai
PY - 2026
DA - 2026/11/02
JO - The Journal of clinical investigation
DO - 10.1172/jci213026
UR - https://europepmc.org/article/MED/42969226
AB - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) arise from hormone-producing cells in the gut and pancreas. Despite increasing incidence of these tumors, therapeutic options remain limited. Well-differentiated GEP-NETs are classified by anatomic site, morphology, and proliferation indices, but this approach offers limited prognostic resolution among phenotypically similar tumors and constrains personalization of treatment decisions. In this issue of the JCI, Karam, Hoffman, and colleagues profiled 38 pancreatic and small-intestinal NETs using joint single-nucleus RNA and ATAC sequencing and projected the resulting malignant cell-associated programs onto matched spatial transcriptomes. Two conserved malignant states emerged: neuronal-like and secretory neuroendocrine. These states span a continuum in both organ sites, are enriched for largely different transcription factor motifs, and occupy distinct microenvironmental niches. Secretory program scores trended higher in metastatic disease and may carry prognostic value. Taken together, these data describe NET heterogeneity as a cell state axis linked to tissue architecture.
SN - 0021-9738
SN - 1558-8238
ER -