Molecular Heterogeneity in Multilobar Low-grade Gliomas

Study Overview
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Brief Summary
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Low-grade diffuse glioma (GDBG) are rare tumors of young adults, whose ontogenesis is poorly understood. Patient management is based on the molecular profile defined by two molecular markers : mutations of the IDH genes and chromosomal 1p19q co-deletion. To date, the IDH and 1p19q statuses are determined on a single fragment collected from the tumor. In the case of GDBGs infiltrating several brain lobes, the sampling is done randomly on only one of the infiltrated lobes. An intra-tumoral heterogeneity of genetic alterations has been suggested and would impact management. Phylogenetic analysis of genetic alterations found, by high throughput sequencing, in each lobe invaded by the same GDBG will make it possible to assess intra-tumoral heterogeneity and to discuss, at a fundamental level, the hypothesis of a single tumor site with secondary diffusion or that of the convergent progression of two or three distinct tumor sites. Clinically, understanding the ontogenesis of GDBGs will improve their management because of the known link between brain location, dominant molecular profile, and prognosis.

Official Title
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Phylogenetic Analysis of Intra-tumor Molecular Heterogeneity on a Pilot Series of Diffuse Low-grade Multilobar Gliomas: Tumor Ontogenesis and Therapeutic Implications

Conditions
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Low-grade Diffuse Glioma

Intervention / Treatment
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* Genetic: sequencing of the complete exome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be over 18 years old. Subject not opposed to participating in the study Be scheduled in the operating room for the first surgery of a low-grade diffuse glioma presupposition on the basis of clinical and imaging criteria. Confirmation, after histopathological analysis of the resected tumor fragments, of the diagnosis of grade II glioma according to the 2016 WHO classification of brain tumors. Exclusion Criteria: Patient minor, or major under legal protection, or unable to give consent. Refusal to participate in the study. Pathology diagnosis of grade III glioma according to WHO 2016 classification Have received oncology treatment (chemotherapy and or chemotherapy) before the first surgery.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: sequencing of the complete exome|Once the pathological diagnosis is confirmed (WHO 2016), a tumor fragment will be selected and frozen for each lobe. DNA extraction will be performed for each fragment. The samples (4 different DNAs per GDBG corresponding to the DNA extracted from each of the 3 lobes and the blood DNA) will be sent to the Montpellier Genomix platform for sequencing of the complete exome.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic profile | exhaustive high throughput sequencing of each of the 3 infiltrated lobes, followed by comparative phylogenetic analysis of the genetic profiles obtained in the 3 locations | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low-grade diffuse glioma, DNA extraction, sequencing