Gene Testing to Help in the Diagnosis and Treatment of Childhood Brain Tumors

Molecular Biology of Pediatric Brain Tumors

RATIONALE: Analyzing the number and structure of genes found in a child's cancer cells may help doctors improve methods of diagnosing and treating children with brain tumors.

PURPOSE: This clinical trial is studying the number and structure of genes in cancer cells of children with brain tumors.

Study Overview

• Status: Completed
• Conditions: Brain Tumors; Central Nervous System Tumors
• Intervention / Treatment: Genetic: cytogenetic analysis; Genetic: comparative genomic hybridization; Genetic: fluorescence in situ hybridization; Genetic: DNA ploidy analysis

Detailed Description

OBJECTIVES:

• Determine the chromosomal gains and losses by DNA ploidy analysis and comparative genomic hybridization in patients with primitive neuroectodermal tumors or medulloblastomas.
• Determine the frequency of specific chromosomal abnormalities, including deletions of chromosomal regions 6, 17, and 22, in these patients.
• Perform a statistical analysis to determine possible associations of chromosomal abnormalities and DNA ploidy with patient age, tumor histology, tumor location, extent of disease, and event-free survival.

OUTLINE: DNA ploidy analysis will be performed to determine the overall level of aneuploidy. The results are compared to the comparative genomic hybridization (CGH) analysis, which is used to demonstrate tumor-specific losses or gains, including amplification, of specific chromosomal regions. Tumors are also screened for specific abnormalities by fluorescent in situ hybridization (FISH), which detects chromosomal rearrangements, including balanced translocations, deletions, amplifications, etc. PCR-based microsatellite polymorphism analysis may also be performed.

Primitive neuroectodermal tumors (PNETs) are screened by FISH with a distal 17p13.3 cosmid and a 17q25 cosmid to identify tumors with a 17p deletion. Atypical teratoid/rhabdoid tumors and PNETs without a 17p deletion are screened by FISH with a series of cosmids from 22q11.2. PNETs are also screened by interphase FISH with cosmids from chromosome 6 to identify tumors with deletions.

Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment.

PROJECTED ACCRUAL: This study will accrue 360 specimens.

• Study Type: Observational
• Enrollment (Actual): 88

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's & Women's Hospital of British Columbia
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3J 3G9
      • IWK Health Centre
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Children's Hospital
  • California
    • Downey, California, United States, 90027
      • Southern California Permanente Medical Group
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Long Beach, California, United States, 90801-1428
      • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90048-1865
      • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    • Madera, California, United States, 93638-8762
      • Children's Hospital Central California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Center for Cancer and Blood Disorders
  • Connecticut
    • Farmington, Connecticut, United States, 06360-2875
      • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
    • Savannah, Georgia, United States, 31403-3089
      • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Illinois
    • Park Ridge, Illinois, United States, 60068-1174
      • Advocate Lutheran General Cancer Care Center
    • Rockford, Illinois, United States, 61104-2315
      • Swedish-American Regional Cancer Center
    • Springfield, Illinois, United States, 62794-9677
      • Simmons Cooper Cancer Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Indianapolis Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Blank Children's Hospital
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40232
      • Kosair Children's Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503-2560
      • Butterworth Hospital at Spectrum Health
    • Kalamazoo, Michigan, United States, 49007-5381
      • CCOP - Kalamazoo
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota
    • St. Paul, Minnesota, United States, 55102-2392
      • Children's Hospitals and Clinics of Minnesota - St. Paul
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89109-2306
      • CCOP - Nevada Cancer Research Foundation
  • New Jersey
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
    • Morristown, New Jersey, United States, 07962
      • Overlook Hospital
    • Morristown, New Jersey, United States, 07962
      • Carol G. Simon Cancer Center at Morristown Memorial Hospital
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5000
      • Rainbow Babies and Children's Hospital
    • Columbus, Ohio, United States, 43205-2696
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404-1815
      • Dayton Children's - Dayton
    • Youngstown, Ohio, United States, 44501
      • Tod Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Children's Hospital
    • Philadelphia, Pennsylvania, United States, 19104-9786
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh of UPMC
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Knoxville, Tennessee, United States, 37901
      • East Tennessee Children's Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine - Amarillo
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • San Antonio, Texas, United States, 78229-3993
      • Methodist Children's Hospital of South Texas
  • Utah
    • Salt Lake City, Utah, United States, 84113-1100
      • Primary Children's Medical Center
  • Washington
    • Spokane, Washington, United States, 99210-0248
      • Deaconess Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Center for Cancer and Blood
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children with primitive neuroectodermal tumors / medulloblastoma (PNET/Mb).

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary CNS malignancy consistent with primitive neuroectodermal tumor, medulloblastoma, or atypical teratoid/rhabdoid tumor
• Must be entered on CCG-9921, CCG-9931, CCG-A9961, CCG-99703 or other front-line studies developed from CCG-90024 or CCG-90025
• Retrospective specimens also obtained from CCG-921, CCG-923, CCG-9892, CCG-9921, and CCG-9931

PATIENT CHARACTERISTICS:

Age:

• Under 21

Performance status:

• See Disease Characteristics

Life expectancy:

• See Disease Characteristics

Hematopoietic:

• See Disease Characteristics

Hepatic:

• See Disease Characteristics

Renal:

• See Disease Characteristics

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description
Frequency of specific chromosomal gains, losses and rearrangements in a series of infratentorial and supratentorial PNETS	Estimate the frequency of specific chromosomal gains, losses and rearrangements in a series of infratentorial and supratentorial PNETS diagnosed in children

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jaclyn A. Biegel, PhD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: December 1, 1996
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): August 6, 2014
• Last Update Submitted That Met QC Criteria: August 5, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: untreated childhood medulloblastoma; untreated childhood supratentorial primitive neuroectodermal tumor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Brain Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: B971; COG-B971 (Other Identifier: Children's Oncology Group); CCG-B971 (Other Identifier: Children's Cancer Group); CDR0000065814 (Other Identifier: Clinical Trials.gov)