Aberrant brain-type neuronal programs in large-cell pancreatic neuroendocrine carcinoma

Debnath, O.; Berger, H.; Detjen, K.; Kirchner, P.; Marinoni, I.; Eichhorn, I.; Bolduan, F.; Conrad, T.; Horst, D.; Eils, R.; Wiedenmann, B.; Perren, A.; Ishaque, N.

doi:10.1101/2025.06.18.660360

bioRxiv · 10.1101/2025.06.18.660360

Aberrant brain-type neuronal programs in large-cell pancreatic neuroendocrine carcinoma

Debnath, O.·Berger, H.·Detjen, K.·Kirchner, P.·Marinoni, I.·Eichhorn, I.·Bolduan, F.·Conrad, T.·Horst, D.·Eils, R.·Wiedenmann, B.·Perren, A.·Ishaque, N.

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Abstract

High-grade pancreatic neuroendocrine carcinoma (panNEC) is a rare, aggressive cancer with limited tissue availability. Single-nucleus transcriptomics of five large-cell panNECs revealed two clinically relevant neuroendocrine cell states: one highly proliferative with an aberrant brain-specific neuronal differentiation program and another stress-responsive state enriched for heat stress, hypoxia, and glycolysis. Our findings suggest potentially new therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.

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Debnath, O., Berger, H., Detjen, K., Kirchner, P., Marinoni, I., Eichhorn, I., Bolduan, F., Conrad, T., Horst, D., Eils, R., Wiedenmann, B., Perren, A., Ishaque, N.. 2025-06-24. Aberrant brain-type neuronal programs in large-cell pancreatic neuroendocrine carcinoma. https://doi.org/10.1101/2025.06.18.660360

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