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Molecular classification of low-grade diffuse gliomas

Kim, Young-Ho and Nobusawa, Sumihito and Mittelbronn, Michel and Paulus, Werner and Brokinkel, Benjamin and Keyvani, Kathy and Sure, Ulrich and Wrede, Karsten and Nakazato, Yoichi and Tanaka, Yuko and Vital, Anne and Mariani, Luigi and Stawski, Robert and Watanabe, Takuya and De Girolami, Umberto and Kleihues, Paul and Ohgaki, Hiroko. (2010) Molecular classification of low-grade diffuse gliomas. American Journal of Pathology, Vol. 177, no. 6. pp. 2708-2714.

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Official URL: http://edoc.unibas.ch/dok/A6003830

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Abstract

The current World Health Organization classification recognizes three histological types of grade II low-grade diffuse glioma (diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma). However, the diagnostic criteria, in particular for oligoastrocytoma, are highly subjective. The aim of our study was to establish genetic profiles for diffuse gliomas and to estimate their predictive impact. In this study, we screened 360 World Health Organization grade II gliomas for mutations in the IDH1, IDH2, and TP53 genes and for 1p/19q loss and correlated these with clinical outcome. Most tumors (86%) were characterized genetically by TP53 mutation plus IDH1/2 mutation (32%), 1p/19q loss plus IDH1/2 mutation (37%), or IDH1/2 mutation only (17%). TP53 mutations only or 1p/19q loss only was rare (2 and 3%, respectively). The median survival of patients with TP53 mutation ± IDH1/2 mutation was significantly shorter than that of patients with 1p/19q loss ± IDH1/2 mutation (51.8 months vs. 58.7 months, respectively; P = 0.0037). Multivariate analysis with adjustment for age and treatment confirmed these results (P = 0.0087) and also revealed that TP53 mutation is a significant prognostic marker for shorter survival (P = 0.0005) and 1p/19q loss for longer survival (P = 0.0002), while IDH1/2 mutations are not prognostic (P = 0.8737). The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and 1p/19q loss has power similar to histological classification and avoids the ambiguity inherent to the diagnosis of oligoastrocytoma.
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
Bibsysno:Link to catalogue
Publisher:American Society for Investigative Pathology
ISSN:0002-9440
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:12
Deposited On:26 Apr 2013 07:00

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