tud
Molecular Mechanisms Associated with Chromosomal and Microsatellite Instability in Sporadic Glioblastoma multiforme
2014-02-12
[Electronic ed.]
4519974-7
Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden
prv
Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, Dresden
male
male
male
male
female
female
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.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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XA 10000
Glioblastom, Glioblastoma multiforme, Tumor, Karzinogenese, Tumorentwicklung, Mismatch-Reparatur, chromosomale Instabilität
Glioblastoma multiforme, Tumorigenesis, Mismatch repair, Chromosomal instability
urn:nbn:de:bsz:14-qucosa-133546
40947245X
10.1159/000079488
Karger
pbl
Karger, Basel
Ramon
Martinez
aut
Hans-K.
Schackert
aut
Jens
Plaschke
aut
Gustavo
Baretton
aut
Hella
Appelt
aut
Gabriele
Schackert
aut
eng
2004
http://dx.doi.org/10.1159/000079488
Volltext des Artikels, der zuerst in der Zeitschrift "Oncology" des Karger-Verlages erschienen ist.
Oncology 2004;66:395–403, ISSN: 0030-2414
born digital
MV
michaela.voigt@slub-dresden.de
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