Academic Journal
Genetic intratumour heterogeneity in digestive high-grade neuroendocrine neoplasms.
| Τίτλος: | Genetic intratumour heterogeneity in digestive high-grade neuroendocrine neoplasms. |
|---|---|
| Συγγραφείς: | Morken S; Cancer Clinic, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Sorbye H; Cancer Clinic, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Deng W; Cancer Clinic, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Dogramaci HT; Cancer Clinic, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Venizelos A; Department of Clinical Science, University of Bergen, Bergen, Norway., Vestermark LW; Department of Oncology, University Hospital of Southern Denmark, Esbjerg, Denmark., Pfeiffer P; Department of Oncology, Odense University Hospital, Odense, Denmark., Hjortland GO; Department of Oncology, Oslo University Hospital, Oslo, Norway., Kersten C; Department of Research, Hospital of Southern Norway, Kristiansand, Norway., Hofsli E; Department of Oncology, St. Olavs Hospital, Trondheim, Norway., Elvebakken H; Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway., Couvelard A; Pathology Department, Bichat Hospital AP-HP and Université Paris Cité, Paris, France., Lothe IMB; Department of Pathology, Oslo University Hospital, Oslo, Norway., Perren A; Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland., Knappskog S; Cancer Clinic, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway. |
| Πηγή: | Journal of neuroendocrinology [J Neuroendocrinol] 2026 Oct; Vol. 38 (10), pp. e70296. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley & Sons Country of Publication: United States NLM ID: 8913461 Publication Model: Print Cited Medium: Internet ISSN: 1365-2826 (Electronic) Linking ISSN: 09538194 NLM ISO Abbreviation: J Neuroendocrinol Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2010->: Malden, MA : Wiley & Sons Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989- |
| Ιατρικοί όροι (MeSH): | Neuroendocrine Tumors*/genetics , Neuroendocrine Tumors*/pathology , Digestive System Neoplasms*/genetics , Digestive System Neoplasms*/pathology , Genetic Heterogeneity*, Humans ; Mutation ; Female ; Male ; Neoplasm Grading |
| Περίληψη: | Digestive high-grade neuroendocrine neoplasms (HG-NEN) are rare and heterogeneous tumours with an aggressive biology and limited treatment efficacy. Genetic intratumour heterogeneity (ITH) is a mechanism of progression and treatment resistance in other cancers, yet unexplored in digestive HG-NEN. Next-generation sequencing with a 360-cancer gene panel was performed on 51 digestive HG-NEN, suitable for multiregional sampling. The mutational status of each sample within a patient was assessed to calculate an ITH-index, defined as the average number of discordant mutations across all pair-wise comparisons between samples. An ITH-index based on primary tumour samples was calculated for chemotherapy-naïve cases: 28 neuroendocrine carcinomas (NEC), 9 mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) and 3 neuroendocrine tumour grade 3 (NET G3). Median ITH-index in NEC/MiNEN was 5, with a wide range (0-98.8). Greater heterogeneity was associated with right-sided colonic primaries (p = .005) and higher tumour mutational burden (r = 0.74, p < .001). Median overall survival was 7 months longer in NEC/MiNEN with median ITH-index above compared to below median (22.5 vs. 15.5 months, p = .077), driven mostly by patients with locoregional disease. Response to first-line chemotherapy was not influenced by median ITH-index. No heterogeneity was found among driver mutations in BRAF and KRAS. NET G3 displayed low heterogeneity (ITH-index 2-3). Higher ITH-index was not associated with shorter survival or treatment response, suggesting that genetic ITH is not the primary resistance mechanism in digestive NEC/MiNEN. Moving towards targeted treatment strategies, our data indicate that a single biopsy may underestimate ITH. BRAF and KRAS may be favourable targets as they displayed no heterogeneity. (© 2026 The Author(s). Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.) |
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| Grant Information: | F-12180 The Western Norway Regional Health Authority; R280-A16006 Nordic Cancer Union; NO1501286042 Novartis; Ipsen; 223271 Norwegian Cancer Society |
| Contributed Indexing: | Keywords: MiNEN; NEC; NET G3; heterogeneity; mutation |
| Entry Date(s): | Date Created: 20261018 Date Completed: 20261018 Latest Revision: 20261020 |
| Update Code: | 20261020 |
| PubMed Central ID: | PMC13677211 |
| DOI: | 10.1111/jne.70296 |
| PMID: | 42893790 |
| Βάση Δεδομένων: | MEDLINE |
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