{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T12:50:59Z","timestamp":1784638259802,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002203","name":"Brain Tumour Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002203","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012353","name":"Deutschen Konsortium f\u00fcr Translationale Krebsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012353","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Although inactivation of the von Hippel\u2013Lindau gene (\n                      <jats:italic>VHL<\/jats:italic>\n                      ) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of\n                      <jats:italic>VHL<\/jats:italic>\n                      mutations in sporadic ELSTs and compare their characteristics to VHL\u2010disease\u2010related tumours.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL\u2010disease\u2010related ELSTs by targeted sequencing and DNA methylation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>VHL<\/jats:italic>\n                      mutations and small deletions detected by targeted deep sequencing were identified in 9\/11 sporadic ELSTs (82%). No other cancer\u2010related genetic pathway was altered except for\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter mutations in two sporadic ELST and one VHL\u2010disease\u2010related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6\/10 (60%) VHL\u2010disease\u2010related and 10\/11 (91%) sporadic ELSTs resulting in biallelic\n                      <jats:italic>VHL<\/jats:italic>\n                      inactivation in 8\/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL\u2010disease\u2010related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52\u00a0years,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001, Fisher's exact test). VHL\u2010disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression\u2010free survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0002, log\u2010rank test).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Biallelic inactivation of\n                      <jats:italic>VHL<\/jats:italic>\n                      is the main mechanism underlying ELSTs, but unknown mechanisms beyond\n                      <jats:italic>VHL<\/jats:italic>\n                      may rarely be involved in the pathogenesis of sporadic ELSTs.\n                    <\/jats:p>\n                  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