Proteomic Characterization of Aggressive Oligodendrogliomas
- Conditions
- Oligodendroglioma
- Interventions
- Other: Proteomic analysis
- Registration Number
- NCT04843085
- Lead Sponsor
- Hospices Civils de Lyon
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
-
- 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)
- opposed patients
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description O1 Proteomic analysis the more aggressive subgroup of oligodendroglioma samples of 30 patients IDH-wildtype glioblastomas Proteomic analysis patients with IDH-wildtype glioblastomas, samples of 15 patients O2 Proteomic analysis subgroup 2 of oligodendroglioma samples of 30 patients IDH-mutant astrocytomas Proteomic analysis patients with IDH-mutant astrocytomas, samples of 15 patients O3 Proteomic analysis subgroup 3 of oligodendroglioma samples of 30 patients
- Primary Outcome Measures
Name Time Method proteomic profiles Baseline (at time of diagnosis surgery) Concordance of the classification of oligodendrogliomas based on their proteomic profiles with our previously identified oligodendrogliomas subgroups.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (2)
Institut du Cerveau et de la Moelle
🇫🇷Paris, France
Groupement Hospitalier Est HCL
🇫🇷Bron, France