Uncovering cell-state heterogeneity in large-cell panNEC indicates potentially targetable aberrant brain type neuronal de-differentiation

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Introduction: Classification and treatment of high-grade pancreatic neuroendocrine carcinoma (panNEC), particularly those with large-cell morphology, present significant clinical challenges due to considerable inter- and intra-patient tumour heterogeneity.

Aim(s): We, therefore, aimed to deeply phenotype large-cell panNEC tissues to establish a reference atlas of this rare and difficult-to-procure tumour and to identify therapeutic targets by characterising tumour heterogeneity and developmental origins, thereby shifting the paradigm from targeting individual molecular markers to pathological cell states.

Materials and methods: To this end, we conducted single-nucleus RNA sequencing (snRNA-seq) analysis of five tumour samples to decode the previously unrecognised cellular landscape of this tumour type.

Conference:

Presenting Author: Debnath O

Authors: Debnath O, Berger H, Detjen K, Kirchner P, Marinoni I,

Keywords: pancreatic neuroendocrine carcinoma, single cell, personalised medicine,