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

Brain Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00899834
• Other study ID #: NBTP02-SJ
• Status: Completed
• Phase: N/A
• First received: May 9, 2009
• Last updated: July 25, 2016
• Start date: June 2006
• Est. completion date: August 2015

Study information

• Verified date: July 2016
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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)

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Glioma
• Neoplasms
• Nervous System Neoplasms

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Stanford University Medical Center	Palo Alto	California
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA gains and losses and RNA expression in tumor samples and normal tissue	Tissue samples will be obtained at autopsy.	at autopsy	No
Primary	Genome-wide expression patterns of RNA in tumor samples and normal tissue as assessed by Affymetrix gene expression profiling	Tissue samples will be obtained at autopsy.	at autopsy	No
Primary	Validation of results of the genome-wide analysis	Tissue samples will be obtained at autopsy.	at autopsy	No
Primary	Mutations in candidate tumor-suppressor genes and oncogenes as assessed by direct sequencing analysis of tumor DNA	Tissue samples will be obtained at autopsy.	at autopsy	No
Primary	Confirmation of the tumor-specific nature of candidate tumor-suppressor gene and oncogene mutation as assessed by the correspondent constitutional DNA	Tissue samples will be obtained at autopsy.	at autopsy	No
Primary	Confirmation of genomic gains or losses as assessed by fluorescence in situ hybridization (FISH) performed on tissue microarray (TMA) using non-neoplastic brain tissue	Tissue samples will be obtained at autopsy.	at autopsy	No
Primary	Protein expression patterns as assessed by immunohistochemistry or western blot compared to normal brain stem tissue	Tissue samples will be obtained at autopsy.	at autopsy	No
Secondary	Assess aspects associated with this procedure, including potential benefits and drawbacks	Tissue samples will be obtained at autopsy.	at autopsy	No

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital