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Analysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study.

2025-09Journal article Restricted access
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dc.contributor.authorGui, Chloe
dc.contributor.authorWang, Justin Z.
dc.contributor.authorPatil, Vikas
dc.contributor.authorLandry, Alexander P.
dc.contributor.authorCastelo-Branco, Pedro
dc.contributor.authorSingh, Olivia
dc.contributor.authorTabori, Uri
dc.contributor.authorAldape, Kenneth
dc.contributor.authorBehling, Felix
dc.contributor.authorBarnholtz-Sloan, Jill S.
dc.contributor.authorHorbinski, Craig
dc.contributor.authorTabatabai, Ghazaleh
dc.contributor.authorAjisebutu, Andrew
dc.contributor.authorLiu, Jeff
dc.contributor.authorPatel, Zeel
dc.contributor.authorYakubov, Rebeca
dc.contributor.authorKaloti, Ramneet
dc.contributor.authorEllenbogen, Yosef
dc.contributor.authorWilson, Christopher
dc.contributor.authorCohen-Gadol, Aaron
dc.contributor.authorTatagiba, Marcos
dc.contributor.authorHolland, Eric C.
dc.contributor.authorSloan, Andrew E.
dc.contributor.authorChotai, Silky
dc.contributor.authorChambless, Lola B.
dc.contributor.authorGao, Andrew
dc.contributor.authorMakarenko, Serge
dc.contributor.authorYip, Stephen
dc.contributor.authorNassiri, Farshad
dc.contributor.authorZadeh, Gelareh
dc.date.accessioned2025-10-03T12:11:05Z
dc.date.available2025-10-03T12:11:05Z
dc.date.issued2025-09
dc.description.abstractBackground TERT promoter mutation is a rare biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival. Although high TERT expression is characteristic of tumours with TERT promoter mutations, it has also been observed in tumours with wildtype TERT promoters. This study aimed to investigate the prevalence and prognostic association of TERT expression in meningiomas.eng
dc.description.abstractThis multi-institutional cohort study retrospectively collected clinical and molecular data from 1241 meningiomas surgically resected between Jan 1, 2000, and Dec 31, 2024, at Toronto Western Hospital, Canada (n=380; discovery cohort) and external institutions in Canada, Germany, and the USA (n=861; validation cohort). All patients were aged 18 years and older. TERT promoter mutation and TERT expression were determined by Sanger and bulk RNA sequencing. The primary outcomes were TERT expression (presence or absence) in meningiomas with and without TERT promoter mutations, and the difference in progression-free survival between tumours expressing TERT and those not expressing TERT. Survival analysis was assessed using Cox regression and Kaplan-Meier analysis.eng
dc.description.abstractBetween Jan 1, 2000, and Dec 31, 2024, clinical demographics and tumour characteristics were collected. Median follow-up was 6·2 years (IQR 1·7-12·5) in the discovery cohort and 3·3 years (1·3-3·8) in the validation cohort. 777 (65·8%) of 1181 patients with sex data in the overall cohort were female; 404 (34·2%) were male. TERT was expressed in 157 (28·7%) of 547 wildtype TERT promoter meningiomas and in 193 (32·0%) of 604 overall with RNA data. TERT expression overall conferred an intermediate progression-free survival, shorter than that in patients with TERT-negative tumours but longer than in those with TERT promoter mutations. In the discovery cohort, median progression-free survival was 3·2 years (95% CI 1·7-6·5) in patients with wildtype TERT promoter tumours expressing TERT, 16·0 years (7·1 to not reached; p=0·0021) in patients with TERT-negative wildtype TERT promoter tumours, and 1·6 years (0·9 to not reached; p=0·039) in patients with TERT promoter mutations. These findings were replicated in the validation cohort. Within each WHO grade, TERT expression conferred a progression-free survival equivalent to TERT-negative meningiomas of one grade higher. Grade 1 tumours with TERT expression had a progression-free survival similar to TERT-negative grade 2 tumours (median not reached [95% CI 16·0 to not reached] vs 8·2 years [95% CI 4·5 to not reached]; p=0·59). Grade 2 tumours with TERT expression had a similar progression-free survival to TERT-negative grade 3 tumours (median 3·6 years [2·4 to 5·3] vs 3·8 years [2·3 to not reached]; p=0·42). Multivariable regression showed that TERT expression remained associated with shorter progression-free survival even after adjusting for TERT promoter mutations, CDKN2A/B loss, chromosome 1p/22q status, and WHO grade (hazard ratio 1·85 [95% CI 1·33-2·57]; p=0·0002).eng
dc.description.sponsorshipRN482811–481519; GN-000430; GN-000693;
dc.identifier.doi10.1016/S1470-2045(25)00267-0
dc.identifier.eissn1474-5488
dc.identifier.issn1470-2045
dc.identifier.other40907516
dc.identifier.urihttp://hdl.handle.net/10400.1/27787
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.rights.uriN/A
dc.titleAnalysis of TERT association with clinical outcome in meningiomas: a multi-institutional cohort study.eng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1203
oaire.citation.issue26
oaire.citation.startPage1191
oaire.citation.titleThe Lancet Oncology
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameCastelo-Branco
person.givenNamePedro
person.identifier.ciencia-idE015-7F8F-5CA1
person.identifier.orcid0000-0002-3453-3978
relation.isAuthorOfPublicationbb25b5ad-1769-42be-a7d3-8fe76215aa23
relation.isAuthorOfPublication.latestForDiscoverybb25b5ad-1769-42be-a7d3-8fe76215aa23

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