Long-term organoid culture of a small intestinal neuroendocrine tumor

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and highly heterogeneous neoplasms whose incidence has
markedly increased over the last decades. A grading system based on the tumor cells' proliferation index predicts high-risk for G3
NETs. However, low-to-intermediate grade (G1/G2) NETs have an unpredictable clinical course that varies from indolent to highly
malignant. Cultures of human cancer cells enable to perform functional perturbation analyses that are instrumental to enhance our
understanding of cancer biology. To date, no tractable and reliable long-term culture of G1/G2 NET has been reported to permit
disease modeling and pharmacological screens. Here, we report of the first long-term culture of a G2 metastatic small intestinal
NET that preserves the main genetic drivers of the tumor and retains expression patterns of the endocrine cell lineage.
Replicating the tissue, this long-term culture showed a low proliferation index, and yet it could be propagated continuously
without dramatic changes in the karyotype. The model was readily available for pharmacological screens using targeted agents
and as expected, showed low tumorigenic capacity in vivo. Overall, this is the first long-term culture of NETs to faithfully
recapitulate many aspects of the original neuroendocrine tumor.EGA study EGAS00001007093