| Autor: |
Willscher, Edith, Hopp, Lydia, Kreuz, Markus, Schmidt, Maria, Hakobyan, Siras, Arakelyan, Arsen, Hentschel, Bettina, Jones, David T. W., Pfister, Stefan M., Loeffler, Markus, Loeffler-Wirth, Henry, Binder, Hans |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Druh dokumentu: |
Článek |
| ISSN: |
2072-6694 |
| Popis: |
Molecular mechanisms of lower-grade (II–III) diffuse gliomas (LGG) are still poorly understood, mainly because of their heterogeneity. They split into astrocytoma- (IDH-A) and oligodendroglioma-like (IDH-O) tumors both carrying mutations(s) at the isocitrate dehydrogenase (IDH) gene and into IDH wild type (IDH-wt) gliomas of glioblastoma resemblance. We generated detailed maps of the transcriptomes and DNA methylomes, revealing that cell functions divided into three major archetypic hallmarks: (i) increased proliferation in IDH-wt and, to a lesser degree, IDH-O; (ii) increased inflammation in IDH-A and IDH-wt; and (iii) the loss of synaptic transmission in all subtypes. Immunogenic properties of IDH-A are diverse, partly resembling signatures observed in grade IV mesenchymal glioblastomas or in grade I pilocytic astrocytomas. We analyzed details of coregulation between gene expression and DNA methylation and of the immunogenic micro-environment presumably driving tumor development and treatment resistance. Our transcriptome and methylome maps support personalized, case-by-case views to decipher the heterogeneity of glioma states in terms of data portraits. Thereby, molecular cartography provides a graphical coordinate system that links gene-level information with glioma subtypes, their phenotypes, and clinical context. |
| Databáze: |
Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
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