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.
Condition or disease | Intervention/treatment |
---|---|
Low-grade Diffuse Glioma | Genetic: sequencing of the complete exome |
Study Type : | Observational |
Estimated Enrollment : | 8 participants |
Observational Model: | Case-Only |
Time Perspective: | Other |
Official Title: | Phylogenetic Analysis of Intra-tumor Molecular Heterogeneity on a Pilot Series of Diffuse Low-grade Multilobar Gliomas: Tumor Ontogenesis and Therapeutic Implications |
Actual Study Start Date : | June 24, 2019 |
Estimated Primary Completion Date : | June 2020 |
Estimated Study Completion Date : | December 2020 |
Tracking Information | |||||
---|---|---|---|---|---|
First Submitted Date | June 25, 2019 | ||||
First Posted Date | June 27, 2019 | ||||
Last Update Posted Date | December 3, 2019 | ||||
Actual Study Start Date | June 24, 2019 | ||||
Estimated Primary Completion Date | June 2020 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures |
Genetic profile [ Time Frame: 12 month ] 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
|
||||
Original Primary Outcome Measures | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures | Not Provided | ||||
Original Secondary Outcome Measures | Not Provided | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title | Molecular Heterogeneity in Multilobar Low-grade Gliomas | ||||
Official Title | Phylogenetic Analysis of Intra-tumor Molecular Heterogeneity on a Pilot Series of Diffuse Low-grade Multilobar Gliomas: Tumor Ontogenesis and Therapeutic Implications | ||||
Brief Summary |
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. |
||||
Detailed Description | Not Provided | ||||
Study Type | Observational | ||||
Study Design | Observational Model: Case-Only Time Perspective: Other |
||||
Target Follow-Up Duration | Not Provided | ||||
Biospecimen | Retention: Samples With DNA Description:
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
|
||||
Sampling Method | Non-Probability Sample | ||||
Study Population | resected tumor fragments, of the diagnosis of grade II glioma according to the 2016 WHO classification of brain tumors. | ||||
Condition | Low-grade Diffuse Glioma | ||||
Intervention | 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.
|
||||
Study Groups/Cohorts | Not Provided | ||||
Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||
Recruitment Information | |||||
Recruitment Status | Unknown status | ||||
Estimated Enrollment |
8 | ||||
Original Estimated Enrollment | Same as current | ||||
Estimated Study Completion Date | December 2020 | ||||
Estimated Primary Completion Date | June 2020 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
|
||||
Sex/Gender |
|
||||
Ages | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers | No | ||||
Contacts | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT04000048 | ||||
Other Study ID Numbers | RECHMPL18_0376 | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
|
||||
IPD Sharing Statement |
|
||||
Responsible Party | University Hospital, Montpellier | ||||
Study Sponsor | University Hospital, Montpellier | ||||
Collaborators | Not Provided | ||||
Investigators | Not Provided | ||||
PRS Account | University Hospital, Montpellier | ||||
Verification Date | June 2019 |