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

• Genome-wide expression patterns of RNA in tumor samples, normal brainstem tissue and cerebrospinal fluid using Affymetrix gene expression profiling [ Time Frame: 4 years ] [ Designated as safety issue: No ]
• Validation of results of the genome-wide analysis [ Time Frame: 4 years ] [ Designated as safety issue: No ]
• Proteomic profiling of tumor, normal brainstem tissue and cerebrospinal fluid [ Time Frame: 4 years ] [ Designated as safety issue: No ]
• Protein expression patterns as assessed by immunohistochemistry and western blot compared to normal brainstem tissue [ Time Frame: 4 years ] [ Designated as safety issue: No ]
• Genome-wide analysis of tumor samples and normal brainstem tissue [ Time Frame: 4 years ] [ Designated as safety issue: No ]
• In vitro and in vivo molecular analysis of collected samples [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  Collected samples will potentially be used for in vitro analysis and generation of animal models of this tumor.

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.

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.

Community sample

• Diffuse Intrinsic Pontine Glioma
• Brainstem Glioma

• Becher OJ, Hambardzumyan D, Walker TR, Helmy K, Nazarian J, Albrecht S, Hiner RL, Gall S, Huse JT, Jabado N, MacDonald TJ, Holland EC. Preclinical evaluation of radiation and perifosine in a genetically and histologically accurate model of brainstem glioma. Cancer Res. 2010 Mar 15;70(6):2548-57. Epub 2010 Mar 2.
• Shrestha B, Nemes P, Nazarian J, Hathout Y, Hoffman EP, Vertes A. Direct analysis of lipids and small metabolites in mouse brain tissue by AP IR-MALDI and reactive LAESI mass spectrometry. Analyst. 2010 Apr;135(4):751-8.

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)