Comprehensive Molecular Analysis of Tumor Samples Derived From Patients With Diffuse Brainstem Glioma - A Pilot Study
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Brain Tumors
- Sponsor
- St. Jude Children's Research Hospital
- Enrollment
- 81
- Locations
- 3
- Primary Endpoint
- DNA gains and losses and RNA expression in tumor samples and normal tissue
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This multi-institutional study will prospectively collect tumor and constitutional tissue samples from patients with diffuse brainstem glioma and other types of brainstem gliomas either during therapy or at autopsy to perform an extensive analysis of genetic and molecular abnormalities in these tumors.
Detailed Description
Since very little is known about the biology of diffuse brainstem glioma, the goal of this protocol is to undertake a systematic analysis of DNA abnormalities, and of RNA and protein expression in prospectively collected fresh-frozen and fixed tumor samples and correspondent normal tissue from patients affected with this tumor. OBJECTIVES: * Perform genome-wide analysis of DNA gains and losses and RNA expression in tumor samples and normal tissue from patients with diffuse brain stem glioma. * Identify regions of genomic gain or loss using either array comparative genomic hybridization or single nucleotide polymorphism arrays. * Investigate genome-wide expression patterns of RNA derived from tumor samples and normal tissue from these patients via Affymetrix gene expression profiling. * Validate the results of the genome-wide analysis by conducting further evaluation of candidate genes or by investigating the expression of relevant gene products at the RNA and protein levels. * Perform analysis of mutations in candidate tumor-suppressor genes and oncogenes (including whole genome sequencing studies) using direct sequence analysis of tumor DNA and confirm the tumor-specific nature of these mutations by analyzing the correspondent constitutional DNA. * Confirm genomic gains or losses identified by means of fluorescence in situ hybridization (FISH) performed on tissue microarray using non-neoplastic brain tissue from each patient as control when available. * Explore protein expression patterns identified by immunohistochemistry or western blot and compare them to normal brain stem tissue. * To obtain a follow-up (questionnaire and/or telephone interview) after autopsy with parent(s), legal guardian(s), or family members of research participants in the United States to assess aspects associated with this procedure, including potential benefits and drawbacks
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
DNA gains and losses and RNA expression in tumor samples and normal tissue
Time Frame: at autopsy
Tissue samples will be obtained at autopsy.
Genome-wide expression patterns of RNA in tumor samples and normal tissue as assessed by Affymetrix gene expression profiling
Time Frame: at autopsy
Tissue samples will be obtained at autopsy.
Validation of results of the genome-wide analysis
Time Frame: at autopsy
Tissue samples will be obtained at autopsy.
Mutations in candidate tumor-suppressor genes and oncogenes as assessed by direct sequencing analysis of tumor DNA
Time Frame: at autopsy
Tissue samples will be obtained at autopsy.
Confirmation of the tumor-specific nature of candidate tumor-suppressor gene and oncogene mutation as assessed by the correspondent constitutional DNA
Time Frame: at autopsy
Tissue samples will be obtained at autopsy.
Protein expression patterns as assessed by immunohistochemistry or western blot compared to normal brain stem tissue
Time Frame: at autopsy
Tissue samples will be obtained at autopsy.
Confirmation of genomic gains or losses as assessed by fluorescence in situ hybridization (FISH) performed on tissue microarray (TMA) using non-neoplastic brain tissue
Time Frame: at autopsy
Tissue samples will be obtained at autopsy.
Secondary Outcomes
- Assess aspects associated with this procedure, including potential benefits and drawbacks(at autopsy)