Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma

Study Overview
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Brief Summary
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The purpose of this study is to prospectively collect specimens from pediatric patients with diffuse intrinsic pontine glioma or brainstem glioma, either during therapy or at autopsy, in order to characterize the molecular abnormalities of this tumor.

Detailed Description
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High grade diffuse intrinsic pontine glioma (DIPG) accounts for approximately 80% of pediatric brainstem tumors and 10% of pediatric brain tumors, and is the most lethal form of brainstem gliomas in children. There is currently no effective therapy to treat these tumors. We hypothesize that this tumor exhibits unique molecular abnormalities leading to altered RNA and protein expression. The aim of this trial is to collect specimens from pediatric patients with diffuse intrinsic pontine glioma including serum, cerebrospinal fluid, urine, brain tumor and other constitutional tissue, during therapy and/or at autopsy. Our goal is to study this tissue to characterize the genetic abnormalities that lead to tumor formation in order to identify key molecules as biomarkers which we can target to design and test new and more effective treatments.

Official Title
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Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma

Conditions
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Diffuse Intrinsic Pontine Glioma, Brainstem Glioma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of any age with clinical and radiologic diagnosis of diffuse intrinsic pontine glioma Patients with other high-grade gliomas originating in the brainstem Patients with focal gliomas (WHO grade I/II) of the brainstem Exclusion Criteria: Patients with any type of infiltrative low grade (WHO grade I and II) or high grade glioma (WHO grade III and IV) originating outside the brainstem Patients harboring primary brainstem tumors with other histologic diagnoses (e.g., PNET)

Ages Eligible for Study
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Maximum Age: 21 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient samples<br>Fresh-frozen and fixed tumor samples, correspondent normal brain tissue samples, cerebrospinal fluid, urine, and serum samples from patients affected with diffuse intrinsic pontine glioma or brainstem glioma | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genome-wide expression patterns of RNA in tumor samples, normal brainstem tissue and cerebrospinal fluid using Affymetrix gene expression profiling | Collected tumor and normal samples will potentially be used for RNA genome-wide expression pattern profiling. | 5 years | 
| Validation of results of the genome-wide analysis | The molecular analysis done on collected samples will be validated through whole genome sequencing. | 5 years | 
| Proteomic profiling of tumor, normal brainstem tissue and cerebrospinal fluid | To obtain full characterization of collected samples, proteomic profiling will be done on tumor and normal samples collected. | 5 years | 
| Protein expression patterns as assessed by immunohistochemistry and western blot compared to normal brainstem tissue | Collected tumor and normal samples will have the immunochemistry and western blot compared to assess protein expression variation. | 5 years | 
| Genome-wide analysis of tumor samples and normal brainstem tissue | To obtain full characterization of collected samples, whole genome sequencing will be done on tumor and normal samples collected. | 5 years | 
| In vitro and in vivo molecular analysis of collected samples | Collected samples will potentially be used for in vitro analysis and generation of animal models of this tumor. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess aspects associated with specimen acquisition, including potential benefits and drawbacks | In an effort to continue to draw knowledge from samples collected, potential benefits and drawbacks from specimen acquisition will be continuously accessed. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BSG, diffuse intrinsic pontine glioma, DIPG, childhood brainstem glioma, pediatric brainstem glioma, brainstem glioma