Academic Journal
Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations
| العنوان: | Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations |
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| المؤلفون: | Tesileanu, C Mircea S, Vallentgoed, Wies R, Sanson, Marc, Taal, Walter, Clement, Paul M, Wick, Wolfgang, Brandes, Alba Ariela, Baurain, Jean Francais, Chinot, Olivier L, Wheeler, Helen, Gill, Sanjeev, Griffin, Matthew, Rogers, Leland, Ruda', Roberta, Weller, Michael, McBain, Catherine, Reijneveld, Jaap, Enting, Roelien H, Caparrotti, Francesca, Lesimple, Thierry, Clenton, Susan, Gijtenbeek, Anja, Lim, Elizabeth, de Vos, Filip, Mulholland, Paul J, Taphoorn, Martin J B, de Heer, Iris, Hoogstrate, Youri, de Wit, Maurice, Boggiani, Lorenzo, Venneker, Sanne, Oosting, Jan, Bovée, Judith V M G, Erridge, Sara, Vogelbaum, Michael A, Nowak, Anna K, Mason, Warren P, Kros, Johan M, Wesseling, Pieter, Aldape, Ken, Jenkins, Robert B, Dubbink, Hendrikus J, Baumert, Brigitta, Golfinopoulos, Vassilis, Gorlia, Thierry, van den Bent, Martin, French, Pim J |
| المساهمون: | Tesileanu, C Mircea S, Vallentgoed, Wies R, Sanson, Marc, Taal, Walter, Clement, Paul M, Wick, Wolfgang, Brandes, Alba Ariela, Baurain, Jean Francai, Chinot, Olivier L, Wheeler, Helen, Gill, Sanjeev, Griffin, Matthew, Rogers, Leland, Ruda', Roberta, Weller, Michael, McBain, Catherine, Reijneveld, Jaap, Enting, Roelien H, Caparrotti, Francesca, Lesimple, Thierry, Clenton, Susan, Gijtenbeek, Anja, Lim, Elizabeth, de Vos, Filip, Mulholland, Paul J, Taphoorn, Martin J B, de Heer, Iri, Hoogstrate, Youri, de Wit, Maurice, Boggiani, Lorenzo, Venneker, Sanne, Oosting, Jan, Bovée, Judith V M G, Erridge, Sara, Vogelbaum, Michael A, Nowak, Anna K, Mason, Warren P, Kros, Johan M, Wesseling, Pieter, Aldape, Ken, Jenkins, Robert B, Dubbink, Hendrikus J, Baumert, Brigitta, Golfinopoulos, Vassili, Gorlia, Thierry, van den Bent, Martin, French, Pim J |
| سنة النشر: | 2021 |
| المجموعة: | Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| مصطلحات موضوعية: | Astrocytoma, Gene expression, Genome-wide DNA methylation, IDH1, IDH2 |
| الوصف: | Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1(R132H) mutations. Patients harbouring IDH1(R132H) mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1(R132H) have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1(R132H) mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33740099; info:eu-repo/semantics/altIdentifier/wos/WOS:000630648200001; volume:141; issue:6; firstpage:945; lastpage:957; numberofpages:13; journal:ACTA NEUROPATHOLOGICA; https://hdl.handle.net/2318/1888072; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85103099135 |
| DOI: | 10.1007/s00401-021-02291-6 |
| الاتاحة: | https://hdl.handle.net/2318/1888072 https://doi.org/10.1007/s00401-021-02291-6 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.307E6A3A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00401-021-02291-6 |
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