Genetic Study of Brain Tumors in Young Children

INI1 Mutation Analysis and Expression Profiling of Embryonal CNS Tumors

RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer.

PURPOSE: Genetic study to understand how genes may be involved in the development of brain tumors in young children.

Study Overview

• Status: Terminated
• Conditions: Central Nervous System Tumor, Pediatric

Detailed Description

OBJECTIVES:

• Determine the frequency and type of deletions and mutations of the INI1 gene in infants with embryonal central nervous system tumors.
• Compare the gene expression profiles in infants with atypical teratoid/rhabdoid tumors vs medulloblastoma or primitive neuroectodermal tumor.

OUTLINE: This is a multicenter study.

Tumor samples are analyzed by fluorescence in situ hybridization (FISH) for deletions of INI1 gene in chromosome band 22q11.2. Tumors without demonstration of deletions of INI1 gene by FISH are examined by polymerase chain reaction (PCR)-based microsatellite analysis for loss of heterozygosity using markers that map to 22q11.2.

DNA from tumor tissue is analyzed for mutations in the exons of the INI1 gene. Isolated matched normal DNA may be analyzed for identification of germline mutations. Parental DNA may be analyzed to identify inherited germline mutations of the INI1 gene.

The patient's physician may receive the results of the genetic testing. The results do not influence the type or duration of treatment.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 25 months.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4318
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030-2399
      • Texas Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Tissue samples from infants (< 3 years old) with histologically confirmed primary intracranial CNS medulloblastoma/PNET, atypical teratoid/rhabdoid tumor, or choroid plexus carcinoma and with no prior chemotherapy, radiotherapy, or treatment from any other investigational agent will be used for this research study. Patients who meet the eligibility criteria, are treated at a PBTC institution that has IRB approval of this study, and consent to the usage of stored tumor specimens for the study objectives constitute the study population.

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary intracranial central nervous system tumor

  • Medulloblastoma
  • Primitive neuroectodermal tumor
  • Atypical teratoid/rhabdoid tumor
  • Choroid plexus carcinoma
• Potential enrollment on PBTC-001 therapeutic protocol

PATIENT CHARACTERISTICS:

Age:

• Under 3

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior steroids allowed

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Other:

• No concurrent investigational agents

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Deletions and mutations of the INI1 gene in infants with AT/RT, medulloblastoma, PNET, or choroid plexus carcinoma

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002 Jan 24;415(6870):436-42. doi: 10.1038/415436a.

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (Actual): August 1, 2004
• Study Completion (Actual): August 1, 2004

Study Registration Dates

• First Submitted: February 2, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 20, 2011
• Last Update Submitted That Met QC Criteria: July 19, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: untreated childhood medulloblastoma; childhood atypical teratoid/rhabdoid tumor; childhood choroid plexus tumor; untreated childhood supratentorial primitive neuroectodermal tumor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: CDR0000068445; PBTC-N03