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

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

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 81

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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)

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA gains and losses and RNA expression in tumor samples and normal tissue	Tissue samples will be obtained at autopsy.	at autopsy
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
Validation of results of the genome-wide analysis	Tissue samples will be obtained at autopsy.	at autopsy
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
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess aspects associated with this procedure, including potential benefits and drawbacks	Tissue samples will be obtained at autopsy.	at autopsy

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Alberto Broniscer, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): July 26, 2016
• Last Update Submitted That Met QC Criteria: July 25, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: adult brain stem glioma; childhood brain stem glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: NBTP02-SJ