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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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sequencing of the complete exome | Genetic | 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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resected tumor fragments, of the diagnosis of grade II glioma according to the 2016 WHO classification of brain tumors.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Catherine Gozé, PharmD, PhD | Contact | 0467335872 | c-goze@chu-montpellier.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Gui de Chauliac | Recruiting | Montpellier | 34295 | France |
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In this pilot study we chose the fronto-temporal-insular GDBG model to study the intra-tumoral heterogeneity of the low-grade gliomas by 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