Alterations in the RB1 pathway in low-grade diffuse gliomas lacking common genetic alterations

Kim, Y. H. and Lachuer, J. and Mittelbronn, M. and Paulus, W. and Brokinkel, B. and Keyvani, K. and Sure, U. and Wrede, K. and Nobusawa, S. and Nakazato, Y. and Tanaka, Y. and Vital, A. and Mariani, L. and Ohgaki, H.. (2011) Alterations in the RB1 pathway in low-grade diffuse gliomas lacking common genetic alterations. Brain pathology, Vol. 21, no. 6. pp. 645-651.

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Official URL: http://edoc.unibas.ch/dok/A6006997

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We recently reported that the vast majority (<90%) of low-grade diffuse gliomas (diffuse astrocytoma, oligoastrocytoma and oligodendroglioma) carry at least one of the following genetic alterations: IDH1/2 mutation, TP53 mutation or 1p/19q loss. Only 7% of cases were triple-negative (ie, lacking any of these alterations). In the present study, array comparative genomic hybridization (CGH) in 15 triple-negative WHO grade II gliomas (eight diffuse astrocytomas and seven oligodendrogliomas) showed loss at 9p21 (p14(ARF) , p15(INK4b) , p16(INK4a) loci) and 13q14-13q32 (containing the RB1 locus) in three and two cases, respectively. Further analyses in 31 triple-negative cases as well as a total of 160 non-triple-negative cases revealed that alterations in the RB1 pathway (homozygous deletion and promoter methylation of the p15(INK4b) , p16(INK4a) and RB1 genes) were significantly more frequent in triple-negative (26%) than in non-triple-negative cases (11%; P?=?0.0371). Multivariate analysis after adjustment for age, histology and treatment showed that RB1 pathway alterations were significantly associated with unfavorable outcome for patients with low-grade diffuse glioma [hazard ratio, 3.024 (1.279-6.631); P?=?0.0057]. These results suggest that a fraction of low-grade diffuse gliomas lacking common genetic alterations may develop through a distinct genetic pathway, which may include loss of cell-cycle control regulated by the RB1 pathway.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Brain Tumor Biology (Mariani)
UniBasel Contributors:Mariani, Luigi
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:44
Deposited On:31 Jan 2014 09:49

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