Academic Journal
Germline pathogenic variants in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms.
| Τίτλος: | Germline pathogenic variants in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms. |
|---|---|
| Συγγραφείς: | Venizelos A; K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Oncology, Haukeland University Hospital, Bergen, Norway., Sorbye H; Department of Oncology, Haukeland University Hospital, Bergen, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Elvebakken H; Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway.; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Perren A; Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland., Lothe IMB; Department of Pathology, Oslo University Hospital, Oslo, Norway., Couvelard A; Department of Pathology, Université Paris Cité and AP-HP, Bichat Hospital, Paris, France., Hjortland GO; Department of Oncology, Oslo University Hospital, Oslo, Norway., Sundlöv A; Departmentt of Oncology, Skåne University Hospital, Lund, Sweden.; Department of Medical Radiation Physics, Lund University, Lund, Sweden., Svensson J; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden., Garresori H; Department of Oncology, Stavanger University Hospital, Stavanger, Norway., Kersten C; Department of Research, Hospital of Southern Norway, Kristiansand, Norway., Hofsli E; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Oncology, St. Olavs Hospital, Trondheim, Norway., Detlefsen S; Department of Pathology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark., Vestermark LW; Department of Oncology, Odense University Hospital, Odense, Denmark., Ladekarl M; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.; Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark., Tabaksblat EM; Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark., Knappskog S; K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.; Department of Oncology, Haukeland University Hospital, Bergen, Norway. |
| Πηγή: | Endocrine-related cancer [Endocr Relat Cancer] 2023 Aug 23; Vol. 30 (10). Date of Electronic Publication: 2023 Aug 23 (Print Publication: 2023). |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BioScientifica Country of Publication: England NLM ID: 9436481 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1479-6821 (Electronic) Linking ISSN: 13510088 NLM ISO Abbreviation: Endocr Relat Cancer Subsets: MEDLINE |
| Imprint Name(s): | Publication: Jan. 2011- : Bristol, UK : BioScientifica Original Publication: Woodlands, Almondsbury, Bristol, UK : Published for the Society of Endocrinology by the Journal of Endocrinology Ltd., 1994- |
| Ιατρικοί όροι (MeSH): | Pancreatic Neoplasms*/genetics , Pancreatic Neoplasms*/pathology , Gastrointestinal Neoplasms*/genetics , Neuroendocrine Tumors*/pathology , Carcinoma, Neuroendocrine*/pathology , Intestinal Neoplasms*/genetics , Intestinal Neoplasms*/pathology , Stomach Neoplasms*/genetics , Stomach Neoplasms*/pathology, Humans ; Germ-Line Mutation |
| Περίληψη: | High-grade gastroenteropancreatic (HG-GEP) neuroendocrine neoplasms (NENs) are highly aggressive cancers. The molecular etiology of these tumors remains unclear, and the prevalence of pathogenic germline variants in patients with HG-GEP NENs is unknown. We assessed sequencing data of 360 cancer genes in normal tissue from 240 patients with HG-GEP NENs; 198 patients with neuroendocrine carcinomas (NECs) and 42 with grade 3 neuroendocrine tumors (NET G3). Applying strict criteria, we identified pathogenic germline variants and compared the frequency with previously reported data from 33 different cancer types. We found a recurrent MYOC variant in three patients and a recurrent MUTYH variant in two patients, indicating that these genes may be important underlying risk factors for HG-GEP NENs when mutated. Further, germline variants were found in canonical tumor-suppressor genes, such as TP53, RB1, BRIP1 and BAP1. Overall, we found that 4.5% of patients with NEC and 9.5% of patients with NET G3 carry germline pathogenic or highly likely pathogenic variants. Applying identical criteria for variant classification in silico to mined data from 33 other cancer types, the median percentage of patients carrying pathogenic or highly likely pathogenic variants was 3.4% (range: 0-17%). The patients with NEC and pathogenic germline variants had a median overall survival of 9 months, similar to what is generally expected for metastatic GEP NECs. A patient with NET G3 and pathogenic MUTYH variant had much shorter overall survival than expected. The fraction of HG-GEP NENs with germline pathogenic variants is relatively high, but still <10%, meaning that that germline mutations cannot be the major underlying cause of HG-GEP NENs. |
| Contributed Indexing: | Keywords: HG-GEP NEN; etiology; germline; pathogenic variants |
| Entry Date(s): | Date Created: 20230706 Date Completed: 20230824 Latest Revision: 20231103 |
| Update Code: | 20260130 |
| DOI: | 10.1530/ERC-23-0057 |
| PMID: | 37410378 |
| Βάση Δεδομένων: | MEDLINE |
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