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Article: TERT promoter mutations contribute to subset prognostication of lower-grade gliomas

TitleTERT promoter mutations contribute to subset prognostication of lower-grade gliomas
Authors
Issue Date2015
Citation
Modern Pathology, 2015, v. 28, n. 2, p. 177-186 How to Cite?
AbstractRecurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) have been found in various cancers including diffuse gliomas. Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. However, the clinical significance of TERT promoter mutations in lower-grade gliomas remains undetermined. The aim of this study is to evaluate the status of TERT promoter and the respective prognostic significance in a cohort of 237 lower-grade gliomas comprising grades II and III astrocytomas, oligodendrogliomas, and oligoastrocytomas. Mutually exclusive mutations in TERT promoter, C228T and C250T, were identified in 16/105 (15%) diffuse astrocytomas, 16/63 (25%) anaplastic astrocytomas, 13/18 (72%) oligodendrogliomas, 3/3 (100%) anaplastic oligodendrogliomas, 17/45 (38%) oligoastrocytomas, and 2/3 (67%) anaplastic oligoastrocytomas. Mutations co-occurred with 1p/19q codeletion (P<0.001) and are associated with oligodendroglial histology (P<0.001). Kaplan-Meier's survival analysis showed that TERT promoter mutation (P=0.037), Isocitrate dehydrogenase (IDH) mutation (P<0.001), and 1p/19q codeletion (P<0.001) were associated with favorable overall survival (OS). In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). Consistent with this observation, in the subset of 97 IDH-mutated astrocytomas, 14 TERT promoter-mutated tumors showed longer PFS (P=0.001) and OS (P=0.001). In contrast, among the subset of 74 IDH wild-type lower-grade gliomas with intact 1p/19q, TERT promoter mutation was associated with shorter PFS (P=0.001) and OS (P=0.001). Similarly, in the subset of 65 IDH wild-type astrocytomas, 16 TERT promoter-mutated tumors exhibited unfavorable PFS (P=0.007) and OS (P=0.008). Our results indicate that when combined with IDH status, TERT promoter mutation contributes to prognostic subgroups of lower-grade astrocytic tumors or 1p/19q intact lower-grade gliomas and this may further refine future molecular classification of lower-grade gliomas.
Persistent Identifierhttp://hdl.handle.net/10722/325284
ISSN
2023 Impact Factor: 7.1
2023 SCImago Journal Rankings: 2.328
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, Aden Ka Yin-
dc.contributor.authorYao, Yu-
dc.contributor.authorZhang, Zhenyu-
dc.contributor.authorChung, Nellie Yuk Fei-
dc.contributor.authorLiu, Joseph Shu Ming-
dc.contributor.authorLi, Kay Ka Wai-
dc.contributor.authorShi, Zhifeng-
dc.contributor.authorChan, Danny Tat Ming-
dc.contributor.authorPoon, Wai Sang-
dc.contributor.authorZhou, Liangfu-
dc.contributor.authorNg, Ho Keung-
dc.date.accessioned2023-02-27T07:31:13Z-
dc.date.available2023-02-27T07:31:13Z-
dc.date.issued2015-
dc.identifier.citationModern Pathology, 2015, v. 28, n. 2, p. 177-186-
dc.identifier.issn0893-3952-
dc.identifier.urihttp://hdl.handle.net/10722/325284-
dc.description.abstractRecurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) have been found in various cancers including diffuse gliomas. Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. However, the clinical significance of TERT promoter mutations in lower-grade gliomas remains undetermined. The aim of this study is to evaluate the status of TERT promoter and the respective prognostic significance in a cohort of 237 lower-grade gliomas comprising grades II and III astrocytomas, oligodendrogliomas, and oligoastrocytomas. Mutually exclusive mutations in TERT promoter, C228T and C250T, were identified in 16/105 (15%) diffuse astrocytomas, 16/63 (25%) anaplastic astrocytomas, 13/18 (72%) oligodendrogliomas, 3/3 (100%) anaplastic oligodendrogliomas, 17/45 (38%) oligoastrocytomas, and 2/3 (67%) anaplastic oligoastrocytomas. Mutations co-occurred with 1p/19q codeletion (P<0.001) and are associated with oligodendroglial histology (P<0.001). Kaplan-Meier's survival analysis showed that TERT promoter mutation (P=0.037), Isocitrate dehydrogenase (IDH) mutation (P<0.001), and 1p/19q codeletion (P<0.001) were associated with favorable overall survival (OS). In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). Consistent with this observation, in the subset of 97 IDH-mutated astrocytomas, 14 TERT promoter-mutated tumors showed longer PFS (P=0.001) and OS (P=0.001). In contrast, among the subset of 74 IDH wild-type lower-grade gliomas with intact 1p/19q, TERT promoter mutation was associated with shorter PFS (P=0.001) and OS (P=0.001). Similarly, in the subset of 65 IDH wild-type astrocytomas, 16 TERT promoter-mutated tumors exhibited unfavorable PFS (P=0.007) and OS (P=0.008). Our results indicate that when combined with IDH status, TERT promoter mutation contributes to prognostic subgroups of lower-grade astrocytic tumors or 1p/19q intact lower-grade gliomas and this may further refine future molecular classification of lower-grade gliomas.-
dc.languageeng-
dc.relation.ispartofModern Pathology-
dc.titleTERT promoter mutations contribute to subset prognostication of lower-grade gliomas-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/modpathol.2014.94-
dc.identifier.pmid25081751-
dc.identifier.scopuseid_2-s2.0-84922024732-
dc.identifier.volume28-
dc.identifier.issue2-
dc.identifier.spage177-
dc.identifier.epage186-
dc.identifier.eissn1530-0285-
dc.identifier.isiWOS:000348956300002-

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