{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:01:06Z","timestamp":1781650866827,"version":"3.54.5"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Hamburg-Eppendorf (UKE)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurogenetics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Vestibular schwannomas (VSs) are benign tumors of the eighth cranial nerve and the hallmark of\n                    <jats:italic>NF2<\/jats:italic>\n                    -related schwannomatosis. However, the majority of these tumors occur sporadically, arising from two inactivating alterations of the\n                    <jats:italic>NF2<\/jats:italic>\n                    gene. In this study, we re-evaluated a total of 29 VSs, each harboring two intragenic pathogenic\n                    <jats:italic>NF2<\/jats:italic>\n                    variants. In the six NF2-associated VSs, the intra-tumor variant frequencies differed substantially. Three of these cases were mosaic, as the pathogenic\n                    <jats:italic>NF2<\/jats:italic>\n                    variants were absent in the corresponding blood. By contrast, in the majority (20\/23, 87%) of sporadic VSs, the allele frequencies of the two pathogenic\n                    <jats:italic>NF2<\/jats:italic>\n                    variants were nearly identical. Nevertheless, in two sporadic VSs, the intra-tumor variant frequencies were clearly divergent, suggesting the presence of cells with only one variant\u2014the one with the higher allele frequency. We hypothesize that divergence in intra-tumor variant frequencies may provide a potential genetic indication for mosaic\n                    <jats:italic>NF2<\/jats:italic>\n                    -related schwannomatosis, even in cases that appear sporadic.\n                  <\/jats:p>","DOI":"10.1007\/s10048-026-00903-5","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T08:37:16Z","timestamp":1777279036000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Divergence in intra-tumor variant frequencies in sporadic vestibular schwannomas as a potential indication for mosaic NF2-related schwannomatosis?"],"prefix":"10.1007","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9919-4551","authenticated-orcid":false,"given":"Lan","family":"Kluwe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabea","family":"Hartung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Rosahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Farschtschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"903_CR1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/neuonc\/noz153","volume":"22","author":"R Goldbrunner","year":"2020","unstructured":"Goldbrunner R, Weller M, Regis J et al (2020) EANO guideline on the diagnosis and treatment of vestibular schwannoma. Neuro Oncol 22:31\u201345","journal-title":"Neuro Oncol"},{"key":"903_CR2","first-page":"354","volume":"117","author":"S Farschtschi","year":"2020","unstructured":"Farschtschi S, Mautner VF, McLean ACL, Schulz A, Friedrich RE, Rosahl SK (2020) The neurofibromatoses. Dtsch Arztebl Int 117:354\u2013360","journal-title":"Dtsch Arztebl Int"},{"key":"903_CR3","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1016\/j.gim.2022.05.007","volume":"24","author":"SR Plotkin","year":"2022","unstructured":"Plotkin SR, Messiaen L, Legius E et al (2022) Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation. Genet Med 24:1967\u20131977","journal-title":"Genet Med"},{"key":"903_CR4","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/j.1399-0004.2007.00778.x","volume":"71","author":"DG Evans","year":"2007","unstructured":"Evans DG, Ramsden RT, Gokhale C, Bowers N, Huson SM, Wallace A (2007) Should NF2 mutation screening be undertaken in patients with an apparently isolated vestibular schwannoma? Clin Genet 71:354\u2013358","journal-title":"Clin Genet"},{"key":"903_CR5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41436-019-0598-7","volume":"22","author":"DG Evans","year":"2020","unstructured":"Evans DG, Hartley CL, Smith PT et al (2020) Incidence of mosaicism in 1055 de novo NF2 cases: much higher than previous estimates with high utility of next-generation sequencing. Genet Med 22:53\u201359","journal-title":"Genet Med"},{"key":"903_CR6","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1136\/jmedgenet-2020-107022","volume":"58","author":"KV Sadler","year":"2021","unstructured":"Sadler KV, Bowers NL, Hartley C et al (2021) Sporadic vestibular schwannoma: a molecular testing summary. J Med Genet 58:227\u2013233","journal-title":"J Med Genet"},{"key":"903_CR7","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.21873\/invivo.13929","volume":"39","author":"M Breun","year":"2025","unstructured":"Breun M, Schulz T, Monoranu CM, Ernestus RI, Matthies C, L\u00f6hr M, Kluwe L (2025) Pathogenic variants and allele loss of the NF2 and LZTR1 gene in sporadic vestibular schwannoma. In Vivo 39:1251\u20131261","journal-title":"In Vivo"},{"key":"903_CR8","doi-asserted-by":"publisher","first-page":"491","DOI":"10.21873\/cgp.20516","volume":"22","author":"M Breun","year":"2025","unstructured":"Breun M, Schulz T, Monoranu CM, Ernestus RI, Matthies C, Hartung T, Kluwe L, Farschtschi S (2025) Similar allele frequencies of two pathogenic *NF2* variants in each of nine sporadic vestibular schwannomas. Cancer Gen Proteomics 22:491\u2013495","journal-title":"Cancer Gen Proteomics"},{"key":"903_CR9","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17030393","volume":"17","author":"JPJ Douwes","year":"2025","unstructured":"Douwes JPJ, van Eijk R, Maas SLN, Jansen JC, Aten E, Hensen EF (2025) Genetic alterations in patients with\u00a0<sc>NF2<\/sc>-related schwannomatosis and sporadic vestibular schwannomas. Cancers (Basel) 17:393","journal-title":"Cancers (Basel)"},{"key":"903_CR10","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1073\/pnas.68.4.820","volume":"68","author":"AG Knudson Jr.","year":"1971","unstructured":"Knudson AG Jr. (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820\u2013823","journal-title":"Proc Natl Acad Sci U S A"},{"key":"903_CR11","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/gcc.21930","volume":"51","author":"L Kluwe","year":"2012","unstructured":"Kluwe L (2012) Allelic drop-out, allele imbalance, or loss of heterozygosity? 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