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A Molecular Predictor Reassesses Classification of Human Grade II/III Gliomas.

Thierry Rème 1, * Jean-Philippe Hugnot 2, 3 Ivan Bièche 4 Valérie Rigau 5 Fanny Burel-Vandenbos 6 Vincent Prévot 7 Marc Baroncini 7, 8 Denys Fontaine 9 Hugues Chevassus 10 Sophie Vacher 4 Rosette Lidereau 4 Hugues Duffau 2, 11 Luc Bauchet 2, 11 Dominique Joubert 12
* Corresponding author
1 Cellules souches normales et cancéreuses
2 INM - Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs
3 UM2 - Université Montpellier 2 - Sciences et Techniques
4 Oncogénétique
5 Département de pathologie et biobanque
6 Service de pathologie
7 JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837
8 Service de neurochirurgie
9 Service de Neurochirurgie
10 CIC - Montpellier
11 Service de neurochirurgie
12 IGF - Institut de Génomique Fonctionnelle
Abstract : Diffuse gliomas are incurable brain tumors divided in 3 WHO grades (II; III; IV) based on histological criteria. Grade II/III gliomas are clinically very heterogeneous and their prognosis somewhat unpredictable, preventing definition of appropriate treatment. On a cohort of 65 grade II/III glioma patients, a QPCR-based approach allowed selection of a biologically relevant gene list from which a gene signature significantly correlated to overall survival was extracted. This signature clustered the training cohort into two classes of low and high risk of progression and death, and similarly clustered two external independent test cohorts of 104 and 73 grade II/III patients. A 22-gene class predictor of the training clusters optimally distinguished poor from good prognosis patients (median survival of 13-20 months versus over 6 years) in the validation cohorts. This classification was stronger at predicting outcome than the WHO grade II/III classification (P≤2.8E-10 versus 0.018). When compared to other prognosis factors (histological subtype and genetic abnormalities) in a multivariate analysis, the 22-gene predictor remained significantly associated with overall survival. Early prediction of high risk patients (3% of WHO grade II), and low risk patients (29% of WHO grade III) in clinical routine will allow the development of more appropriate follow-up and treatments.
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https://www.hal.inserm.fr/inserm-00840252
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INSERM | CNRS | FNCLCC | CURIE | BS | UNIV-MONTPELLIER | PSL | UNIV-LILLE

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Thierry Rème, Jean-Philippe Hugnot, Ivan Bièche, Valérie Rigau, Fanny Burel-Vandenbos, et al.. A Molecular Predictor Reassesses Classification of Human Grade II/III Gliomas.. PLoS ONE, Public Library of Science, 2013, 8 (6), pp.e66574. ⟨10.1371/journal.pone.0066574⟩. ⟨inserm-00840252⟩

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