Trial Information

Comprehensive Molecular Analysis of Tumor Samples Derived From Patients With Diffuse Brainstem Glioma - A Pilot Study

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