Electronic Resource
MGMT methylation pattern of long-term and short-term survivors of glioblastoma reveals CpGs of the enhancer region to be of high prognostic value
| العنوان: | MGMT methylation pattern of long-term and short-term survivors of glioblastoma reveals CpGs of the enhancer region to be of high prognostic value |
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| المؤلفون: | Leske, Henning; https://orcid.org/0000-0002-3057-8730, Camenisch Gross, Ulrike, Hofer, Silvia, Neidert, Marian Christoph; https://orcid.org/0000-0003-2828-4706, Leske, Sabine, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Lehnick, Dirk, Rushing, Elisabeth Jane |
| المصدر: | Leske, Henning; Camenisch Gross, Ulrike; Hofer, Silvia; Neidert, Marian Christoph; Leske, Sabine; Weller, Michael; Lehnick, Dirk; Rushing, Elisabeth Jane (2023). MGMT methylation pattern of long-term and short-term survivors of glioblastoma reveals CpGs of the enhancer region to be of high prognostic value. Acta Neuropathologica Communications, 11(1):139. |
| بيانات النشر: | BioMed Central 2023-08-28 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Treatment with the alkylating agent temozolomide is known to be prognostically beneficial in a subset of glioblastoma patients. Response to such chemotherapeutic treatment and the prognostic benefit have been linked to the methylation status of O$^{6}$-methylguanine-DNA methyltransferase (MGMT). To date, it has not been entirely resolved which methylation pattern of MGMT is most relevant to predict response to temozolomide treatment and outcome. In this retrospective study, we compared the methylation patterns, analyzed by Sanger sequencing, of 27 isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients that survived more than 3 years (long-term survivors) with those of 24 patients who survived less than a year after initial surgery (short-term survivors). Random Forest-, Correlation-, and ROC-curve analyses were performed. The data showed that MGMT is typically methylated in long-term survivors, whereas no prominent methylation is observed in short-term survivors. The methylation status of CpGs, especially in the promoter and exon1/enhancer region correlated highly with outcome. In addition, age and temozolomide treatment were strongly associated with overall survival. Some CpGs in the enhancer region, in particular CpG 86 (bp + 154), demonstrated high values associated with overall survival in the Random Forest analysis. Our data confirm previously published prognostic factors in IDH-wildtype glioblastoma patients, including age and temozolomide treatment as well as the global MGMT methylation status. The area frequently used for decision making to administer temozolomide at the end of exon1 of MGMT, was associated with outcome. However, our data also suggest that the enhancer region, especially CpG 86 (bp + 154) is of strong prognostic value. Therefore, we propose further investigation of the enhancer region in a large prospective study in order to confirm our findings, which might result in an optimized prediction of survival in glioblastoma patients, likel |
| مصطلحات الفهرس: | Clinic for Neurology, 610 Medicine & health, Enhancer; Glioblastoma; MGMT; Prognosis; Survival; Temozolomide, Journal Article, PeerReviewed, info:eu-repo/semantics/article, info:eu-repo/semantics/publishedVersion |
| URL: | 10.1186/s40478-023-01622-w |
| الاتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess Creative Commons: Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf info:doi/10.5167/uzh-239862 English English |
| Other Numbers: | CHUZH oai:www.zora.uzh.ch:239862 https://www.zora.uzh.ch/id/eprint/239862/1/s40478_023_01622_w.pdf info:doi/10.5167/uzh-239862 info:doi/10.1186/s40478-023-01622-w info:pmid/37641156 urn:issn:2051-5960 1443055137 |
| المصدر المساهم: | HAUPTBIBLIOTHEK UNIV OF ZURICH From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1443055137 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |