{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:37:38Z","timestamp":1786113458240,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008262","name":"Harboefonden","doi-asserted-by":"publisher","award":["17143"],"award-info":[{"award-number":["17143"]}],"id":[{"id":"10.13039\/501100008262","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Von Hippel\u2013Lindau disease (vHL) predisposes to tumor development, mainly clear cell renal carcinoma and hemangioblastoma. The underlying cause is germline variants in the\n                    <jats:italic>VHL<\/jats:italic>\n                    gene, with tumorigenesis thought to require additional somatic \u2018second\u2010hit\u2019 events that most commonly include loss of 3p. However, the precise mechanisms of vHL\u2010related tumor development remain incompletely understood. Genomic investigations of familial hemangioblastoma may help elucidate the early steps of tumorigenesis and contribute to improved disease prediction, biomarker discovery, and therapeutic strategies. We performed whole exome sequencing on 22 familial hemangioblastomas from 7 patients representing 5 unrelated families, and with 4 different causative\n                    <jats:italic>VHL<\/jats:italic>\n                    genotypes. The tumors exhibited low overall mutational burden but showed frequent loss of heterozygosity on chromosome 3 or 3p and single nucleotide variants in the\n                    <jats:italic>VHL<\/jats:italic>\n                    region. Variants were significantly enriched in genes associated with GABAergic and serotonergic neuronal cell types, as well as in pathways regulating cell cycle and neurogenesis. These findings suggest that, in addition to\n                    <jats:italic>VHL<\/jats:italic>\n                    loss, dysregulation of neuronal differentiation programs and cell cycle control may play important roles in hemangioblastoma tumorigenesis.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70228","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T16:42:32Z","timestamp":1774284152000},"page":"2023-2039","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Somatic mutational landscape in von Hippel\u2013Lindau familial hemangioblastoma"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2505-6863","authenticated-orcid":false,"given":"Maja","family":"Dembic","sequence":"first","affiliation":[{"name":"Clinical Genome Center, Department of Clinical Research University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"N\u00f8rrem\u00f8lle","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian Bomme","family":"Ousager","sequence":"additional","affiliation":[{"name":"Clinical Genome Center, Department of Clinical Research University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"van Brakel Andersen","sequence":"additional","affiliation":[{"name":"Clinical Genome Center, Department of Clinical Research University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Louise M\u00f8lgaard","family":"Binderup","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Clinical Genome Center, Department of Clinical Research University of Southern Denmark  Odense Denmark"},{"name":"Department of Clinical Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S190753"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104538"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2006.105.2.248"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3171\/2014.1.JNS131431"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2003.98.1.0082"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2020.05.019"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3844"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.173"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618\u2010017\u20100683\u20101"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40142\u2010019\u201000180\u20109"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20704"},{"key":"e_1_2_11_13_1","first-page":"765","article-title":"Somatic 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