- AutorIn
- Ramon Martinez
- Hans-K. Schackert
- Jens Plaschke
- Gustavo Baretton
- Hella Appelt
- Gabriele Schackert
- Titel
- Molecular Mechanisms Associated with Chromosomal and Microsatellite Instability in Sporadic Glioblastoma multiforme
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa-133546
- Quellenangabe
- Oncology 2004;66:395–403, ISSN: 0030-2414
- Erstveröffentlichung
- 2004
- Abstract (DE)
- Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
- Abstract (EN)
- Objective: Two chromosomal instability (CIN) pathways are described in glioblastoma multiforme (GBM), type 1 and type 2, which can be observed in up to 70% of the cases. Microsatellite instability (MSI) plays a pathogenic role in sporadic cancers such as colon, gastric and endometrial carcinomas with deficient mismatch repair (MMR). We aimed to perform a comprehensive analysis of the relationship between CIN and MSI mechanisms in sporadic glioblastomas. Methods: 129 GBMs were examined (109 newly diagnosed and 20 relapses) investigating MSI, immunohistochemical expression of MMR proteins as well as sequencing and promoter methylation of hMLH1. We characterized the molecular changes frequently correlated with CIN in MSI+ GBMs and compared them with 26 microsatellite-stable tumors. Results: Low-level MSI was observed in 11 of 129 (8.5%) cases and was higher in relapses than in primary GBMs (25 vs. 5.5%, p = 0.027). High-level MSI was not found in any case. A deficient expression of MLH1 and PMS2 without hMLH1 inactivation was observed only in one giant cell GBM. 55% of the MSI+ GBMs showed a profile which did not correspond to one of the known CIN pathways. An inverse association was observed between MSI and mutations of both p53 and PTEN. Conclusions: Our data suggest that CIN and MSI contribute to the genomic instability in GBMs via independent pathways. Since MSI was significantly more frequent in relapses, it might play a role in the malignant progression of GBM.
- Andere Ausgabe
- DOI: 10.1159/000079488
- Volltext des Artikels, der zuerst in der Zeitschrift "Oncology" des Karger-Verlages erschienen ist.
Link: http://dx.doi.org/10.1159/000079488 - Freie Schlagwörter (DE)
- Glioblastom, Glioblastoma multiforme, Tumor, Karzinogenese, Tumorentwicklung, Mismatch-Reparatur, chromosomale Instabilität
- Freie Schlagwörter (EN)
- Glioblastoma multiforme, Tumorigenesis, Mismatch repair, Chromosomal instability
- Klassifikation (DDC)
- 610
- Klassifikation (RVK)
- XA 10000
- Verlag
- Karger, Basel
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa-133546
- Veröffentlichungsdatum Qucosa
- 12.02.2014
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis