Proteomic Characterization of Aggressive Oligodendrogliomas (PROGLIO)

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.

Study Overview

• Status: Recruiting
• Conditions: Oligodendroglioma
• Intervention / Treatment: Other: Proteomic analysis

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: François Ducray, MD; Phone Number: 04 72 35 78 06; Email: francois.ducray@chu-lyon.fr

Study Locations

• France
  • Bron, France
    • Recruiting
    • Groupement Hospitalier Est HCL
    • Contact: François Ducray, MD; Phone Number: 04 72 35 78 06; Email: francois.ducray@chu-lyon.fr
  • Paris, France
    • Not yet recruiting
    • Institut du Cerveau et de la Moelle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

samples of patients with oligodendrolioma, astrocytoma, glioblastoma and normal brain available in the POLA network biobank or the OncoNeuroTek tumor bank (Institut du Cerveau et de la Moelle Épinière)

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
O1; the more aggressive subgroup of oligodendroglioma samples of 30 patients	Other: 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
O2; subgroup 2 of oligodendroglioma samples of 30 patients	Other: 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
O3; subgroup 3 of oligodendroglioma samples of 30 patients	Other: 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
IDH-mutant astrocytomas; patients with IDH-mutant astrocytomas, samples of 15 patients	Other: 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
IDH-wildtype glioblastomas; patients with IDH-wildtype glioblastomas, samples of 15 patients	Other: 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Oligodendroglioma; proteomic analysis; POLA network
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Oligodendroglioma
• Other Study ID Numbers: 69HCL20_0074

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No