Proteomic Characterization of Aggressive Oligodendrogliomas

NCT ID: NCT04843085

Last Updated: 2021-04-13

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2023-09-30

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.

Conditions

Oligodendroglioma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

O1

the more aggressive subgroup of oligodendroglioma samples of 30 patients

Proteomic analysis

Intervention Type: OTHER

: 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

O2

subgroup 2 of oligodendroglioma samples of 30 patients

Proteomic analysis

Intervention Type: OTHER

: 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

O3

subgroup 3 of oligodendroglioma samples of 30 patients

Proteomic analysis

Intervention Type: OTHER

: 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

IDH-mutant astrocytomas

patients with IDH-mutant astrocytomas, samples of 15 patients

Proteomic analysis

Intervention Type: OTHER

: 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

IDH-wildtype glioblastomas

patients with IDH-wildtype glioblastomas, samples of 15 patients

Proteomic analysis

Intervention Type: OTHER

: 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

Interventions

Proteomic analysis

: 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

Intervention Type: OTHER

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Groupement Hospitalier Est HCL

Bron, , France

Site Status: RECRUITING

Institut du Cerveau et de la Moelle

Paris, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

François DUCRAY, MD

Role: CONTACT

francois.ducray@chu-lyon.fr

04 72 35 78 06

Facility Contacts

François Ducray, MD

Role: primary

francois.ducray@chu-lyon.fr

04 72 35 78 06

Other Identifiers

69HCL20_0074

Identifier Type: -

Identifier Source: org_study_id