DNA Analysis of Tumor Tissue Samples From Patients With Diffuse Brain Stem Glioma

Sponsor

St. Jude Children's Research Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00899834

Collaborator

(none)

Enrollment

Locations

110

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors Central Nervous System 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

Study Design

Study Type:

Observational

Actual Enrollment :

81 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Jun 1, 2006

Actual Primary Completion Date :

Aug 1, 2015

Actual Study Completion Date :

Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Tumor Samples fresh-frozen and fixed tumor samples and correspondent normal tissue from patients affected with this tumor.(peripheral blood is applicable only to patients with focal brainstem gliomas and patients who undergo biopsy of a diffuse brainstem glioma at diagnosis)

Outcome Measures

Primary Outcome Measures

DNA gains and losses and RNA expression in tumor samples and normal tissue [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 [at autopsy]
Tissue samples will be obtained at autopsy.
Validation of results of the genome-wide analysis [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 [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 [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 [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 [at autopsy]
Tissue samples will be obtained at autopsy.

Secondary Outcome Measures

Assess aspects associated with this procedure, including potential benefits and drawbacks [at autopsy]
Tissue samples will be obtained at autopsy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Patients of any age with clinical and radiologic diagnosis of diffuse brainstem glioma
Patients with other high-grade gliomas originating in the brainstem
Patients with focal gliomas (WHO grade I/II) of the brainstem
Enrollment in the current version of the St. Jude Tissue Bank protocol for patients whose tissue samples were obtained at diagnosis and who received treatment at St. Jude Children's Research Hospital (SJCRH), or correspondent tissue banking consent for patients treated in other institutions if tissue was obtained prior to death (as applicable, depending on the standard of each institution)

Exclusion Criteria

Patients with any type of infiltrative low-grade (WHO grade 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Palo Alto	California	United States	94305
2	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
3	Seattle Children's Hospital	Seattle	Washington	United States	98105