Proteomic Characterization of Aggressive Oligodendrogliomas

Study Overview
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Brief Summary
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Oligodendrogliomas represent a distinct subgroup of adult gliomas characterized by specific molecular alterations (1p/19q codeletion, mutations of IDH, TERT promoter, CIC, FUBP1). These tumors account for 5 to 10% of adult gliomas and are of special relevance in the neuro-oncology field because of their frequent chemosensitivity (Louis et al. 2016). The genetics of oligodendrogliomas is relatively well characterized but the mechanisms of oncogenesis for these tumors are poorly understood. Although oligodendrogliomas prognosis is usually better than that of other adult glioma subtypes, it remains heterogeneous and there is no effective treatment at recurrence after radiotherapy and chemotherapy. Our recent work conducted within the INCa-funded national POLA network has related this clinical heterogeneity to inter-tumoral heterogeneity. Based on a transcriptomic analysis of a large series of oligodendroglial gliomas we identified 3 subgroups, the most aggressive group being characterized by aggressive clinical and molecular pattern. Recent studies, however, have shown a relatively low level of concordance between mRNA and protein expression, emphasizing the need to use proteomic-based approaches to better understand tumor biology. Taking advantage of the POLA cohort, we propose to expand our previous analysis by integrating a proteomic analysis of oligodendrogliomas. The aim of this project is to identify drivers of oligodendroglioma subgroups, among which potential druggable targets (i.e receptors, metabolism effectors). For this purpose, the proteomic profiles of 90 oligodendrogliomas will be generated and integrated with transcriptomic, genomic and methylation profiles in order to identify signaling pathways specifically associated with each subtype, especially with the most aggressive one. Associations will be explored between candidate signaling pathways expression and clinical outcomes (survival, progression-free survival, objective response). The relevance of the 2 most promising candidate signaling pathways will be assessed in vitro and in vivo using genetically relevant mouse and xenograft models. Our project will identify targetable oncogenic pathways associated with poor prognosis that could lead to new therapeutic strategies.

Official Title
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Proteomic Characterization of Aggressive Oligodendrogliomas

Conditions
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Oligodendroglioma

Intervention / Treatment
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* Other: Proteomic analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - transcriptomic (microarray) data available or possible to obtain them, methylation (450K) data available or possible to obtain them, genomic (SNP array) data available or possible to obtain them, sufficient material for proteomic analysis (frozen tumor samples) Exclusion Criteria: opposed patients
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| O1<br>the more aggressive subgroup of oligodendroglioma samples of 30 patients | Other: Proteomic analysis<br>* : Proteomic analysis in the 3 subgroups of oligodendrogliomas (O1, O2 and O3) and in the comparator groups of IDH-mutant astrocytomas, IDH-wildtype glioblastomas and normal brain samples<br>|
| O2<br>subgroup 2 of oligodendroglioma samples of 30 patients | Other: Proteomic analysis<br>* : Proteomic analysis in the 3 subgroups of oligodendrogliomas (O1, O2 and O3) and in the comparator groups of IDH-mutant astrocytomas, IDH-wildtype glioblastomas and normal brain samples<br>|
| O3<br>subgroup 3 of oligodendroglioma samples of 30 patients | Other: Proteomic analysis<br>* : Proteomic analysis in the 3 subgroups of oligodendrogliomas (O1, O2 and O3) and in the comparator groups of IDH-mutant astrocytomas, IDH-wildtype glioblastomas and normal brain samples<br>|
| IDH-mutant astrocytomas<br>patients with IDH-mutant astrocytomas, samples of 15 patients | Other: Proteomic analysis<br>* : Proteomic analysis in the 3 subgroups of oligodendrogliomas (O1, O2 and O3) and in the comparator groups of IDH-mutant astrocytomas, IDH-wildtype glioblastomas and normal brain samples<br>|
| IDH-wildtype glioblastomas<br>patients with IDH-wildtype glioblastomas, samples of 15 patients | Other: Proteomic analysis<br>* : Proteomic analysis in the 3 subgroups of oligodendrogliomas (O1, O2 and O3) and in the comparator groups of IDH-mutant astrocytomas, IDH-wildtype glioblastomas and normal brain samples<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proteomic profiles | Concordance of the classification of oligodendrogliomas based on their proteomic profiles with our previously identified oligodendrogliomas subgroups. | Baseline (at time of diagnosis surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligodendroglioma, proteomic analysis, POLA network