{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:31:25Z","timestamp":1767861085127,"version":"3.49.0"},"reference-count":18,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Neurol. Sci."],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>ABSTRACT:<\/jats:title>\n                  <jats:sec id=\"S0317167123002536_as1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Isocitrate dehydrogenase (IDH) mutation status is a key diagnostic and prognostic feature of gliomas. It is thought to occur early in glioma tumorigenesis and remain stable over time. However, there are reports documenting a loss of IDH mutation status in a subset of patients with glioma recurrence. Here, we identified patients with a documented loss of IDH mutation status longitudinally and performed multi-platform analysis in order to determine if IDH mutations are stable throughout glioma evolution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0317167123002536_as2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We retrospectively identified patients from our institution from 2009 to 2018 with immunohistochemistry (IHC)-recorded IDH mutation status changes longitudinally. Archived formalin-fixed paraffin-embedded and frozen tissue samples from these patients were collected from our institution\u2019s tumour bank. Samples were analysed using methylation profiling, copy number variation, Sanger sequencing, droplet digital PCR (ddPCR) and IHC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0317167123002536_as3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We reviewed 1491 archived glioma samples including 78 patients with multiple IDH mutant tumour samples collected longitudinally. In all instances of documented loss of IDH mutation status, multi-platform profiling identified a mixture of low tumour cell content and non-neoplastic tissue including perilesional, reactive or inflammatory cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0317167123002536_as4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>All patients with a documented loss of IDH mutation status longitudinally were resolved through multi-platform analysis. These findings support the hypothesis that IDH mutations occur early in gliomagenesis and in the absence of copy number changes at the IDH loci and are stable throughout tumour treatment and evolution. Our study highlights the importance of accurate surgical sampling and the role of DNA methylome profiling in diagnostically uncertain cases for integrated pathological and molecular diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/cjn.2023.253","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T03:12:52Z","timestamp":1689131572000},"page":"362-368","source":"Crossref","is-referenced-by-count":1,"title":["Methylation Profiling Identifies Stability of Isocitrate Dehydrogenase Mutation Over Time"],"prefix":"10.1017","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1191-9579","authenticated-orcid":false,"given":"Mathew R.","family":"Voisin","sequence":"first","affiliation":[{"name":"University of Toronto"},{"name":"University Health Network and University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6685-1970","authenticated-orcid":false,"given":"Chloe","family":"Gui","sequence":"additional","affiliation":[{"name":"University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikas","family":"Patil","sequence":"additional","affiliation":[{"name":"University Health Network and University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2204-3277","authenticated-orcid":false,"given":"Andrew F.","family":"Gao","sequence":"additional","affiliation":[{"name":"University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gelareh","family":"Zadeh","sequence":"additional","affiliation":[{"name":"University of Toronto"},{"name":"University Health Network and University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"S0317167123002536_ref17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1775-1"},{"key":"S0317167123002536_ref13","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164382"},{"key":"S0317167123002536_ref1","first-page":"1231","article-title":"The 2021 WHO classification of tumors of the central nervous system: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Dev Oncol"},{"key":"S0317167123002536_ref3","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nos317"},{"key":"S0317167123002536_ref15","doi-asserted-by":"publisher","DOI":"10.1038\/nature26000"},{"key":"S0317167123002536_ref16","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00367"},{"key":"S0317167123002536_ref10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708914114"},{"key":"S0317167123002536_ref2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.43.2674"},{"key":"S0317167123002536_ref7","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-012-0844-1"},{"key":"S0317167123002536_ref11","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv127"},{"key":"S0317167123002536_ref18","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000702"},{"key":"S0317167123002536_ref14","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0595-z"},{"key":"S0317167123002536_ref5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.21.9832"},{"key":"S0317167123002536_ref9","doi-asserted-by":"publisher","DOI":"10.3171\/2014.9.FOCUS14505"},{"key":"S0317167123002536_ref4","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0777-8"},{"key":"S0317167123002536_ref6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407279"},{"key":"S0317167123002536_ref12","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-0814-x"},{"key":"S0317167123002536_ref8","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080958"}],"container-title":["Canadian Journal of Neurological Sciences \/ Journal Canadien des Sciences Neurologiques"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0317167123002536","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T02:20:18Z","timestamp":1767838818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0317167123002536\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,12]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["S0317167123002536"],"URL":"https:\/\/doi.org\/10.1017\/cjn.2023.253","relation":{},"ISSN":["0317-1671","2057-0155"],"issn-type":[{"value":"0317-1671","type":"print"},{"value":"2057-0155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,12]]}}}