The C250T mutation of TERTp might grant a better prognosis to glioblastoma by exerting less biological effect on telomeres and chromosomes than the C228T mutation

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  • dc.contributor.author Gorria, Teresa
  • dc.contributor.author Crous-Bou, Marta
  • dc.contributor.author Pineda, Estela
  • dc.contributor.author Hernandez, Ainhoa
  • dc.contributor.author Domenech, Marta
  • dc.contributor.author Sanz, Carolina
  • dc.contributor.author Jares, Pedro
  • dc.contributor.author Muñoz Mármol, Ana María
  • dc.contributor.author Arpí Llucià, Oriol
  • dc.contributor.author Meléndez, Bárbara
  • dc.contributor.author Gut, Marta
  • dc.contributor.author Esteve, Anna
  • dc.contributor.author Esteve-Codina, Anna
  • dc.contributor.author Parra Farré, Genís
  • dc.contributor.author Alameda Quitllet, Francisco
  • dc.contributor.author Carrato, Cristina
  • dc.contributor.author Aldecoa, Iban
  • dc.contributor.author Mallo, Mar
  • dc.contributor.author Iglesia, Nuria de la
  • dc.contributor.author Balana, Carmen
  • dc.date.accessioned 2024-10-08T06:26:20Z
  • dc.date.available 2024-10-08T06:26:20Z
  • dc.date.issued 2024
  • dc.description.abstract The aim of this study was to determine how TERTp mutations impact glioblastoma prognosis. Materials and methods: TERTp mutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients. Results: Overall, there were no differences in outcomes between patients with mutated TERTp-wt or TERTp. However, we found significant differences according to the type of TERTp mutation. Progression-free survival (mPFS) was 9.1 months for those with the C250T mutation and 7 months for those with either the C228T mutation or TERTp-wt (p = 0.016). Overall survival (mOS) was 21.9 and 15 months, respectively (p = 0.026). This differential effect was more pronounced in patients with MGMTp methylation (mPFS: p = 0.008; mOS: p = 0.021). Multivariate analysis identified the C250T mutation as an independent prognostic factor for longer mOS (HR 0.69; p = 0.044). We found no differences according to TERTp mutation status in molecular alterations common in glioblastoma, nor in copy number variants in genes related to alternative lengthening of telomeres. Nevertheless, in the gene enrichment analysis adjusted for MGMTp methylation status, some Reactome gene sets were differentially enriched, suggesting that the C250T mutation may exert a lesser effect on telomeres or chromosomes. Conclusions: In our series, patients exhibiting the C250T mutation had a more favorable prognosis compared to those with either TERPp-wt or TERTp C228T mutations. Additionally, our findings suggest a reduced involvement of the C250T mutation in the underlying biological mechanisms related to telomeres.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Gorria T, Crous C, Pineda E, Hernandez A, Domenech M, Sanz C, et al. The C250T mutation of TERTp might grant a better prognosis to glioblastoma by exerting less biological effect on telomeres and chromosomes than the C228T mutation. Cancers (Basel). 2024 Feb 9;16(4):735. DOI: 10.3390/cancers16040735
  • dc.identifier.doi http://dx.doi.org/10.3390/cancers16040735
  • dc.identifier.issn 2072-6694
  • dc.identifier.uri http://hdl.handle.net/10230/61341
  • dc.language.iso eng
  • dc.publisher MDPI
  • dc.relation.ispartof Cancers (Basel). 2024 Feb 9;16(4):735
  • dc.rights © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword MGMTp methylation
  • dc.subject.keyword RNA-Seq differential expression analysis
  • dc.subject.keyword TERTp mutations
  • dc.subject.keyword Glioblastoma
  • dc.subject.keyword Whole-exome sequencing
  • dc.title The C250T mutation of TERTp might grant a better prognosis to glioblastoma by exerting less biological effect on telomeres and chromosomes than the C228T mutation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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