Studying Tumor Samples From Young Patients With Neuroblastoma
Recruitment status was Active, not recruiting
RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.
PURPOSE: This research study is looking at tumor samples from young patients with neuroblastoma.
Genetic: DNA analysis
Genetic: mutation analysis
Genetic: nucleic acid sequencing
Genetic: polymerase chain reaction
Genetic: polymorphism analysis
|Official Title:||Characterizing the Frequency and Spectrum of ALK Mutations in Neuroblastoma|
- Event-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Disease progression as assessed by International Neuroblastoma Response Criteria [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
|Estimated Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
- To comprehensively identify and characterize the spectrum and frequency of mutations in ALK across all neuroblastoma disease subsets using methodologies that will be resource neutral to the Children's Oncology Group Neuroblastoma Nucleic Acids Bank.
- To formulate genetic screening recommendations for newly diagnosed patients with or without a family history of neuroblastoma.
- To identify the functionally relevant ALK mutations that can be pharmacologically inhibited.
- To test for the prognostic capability of ALK alterations.
- To determine the clinical significance of ALK mutations and/or genomic rearrangements by combining ALK mutation, amplification, and translocation data overall and within each neuroblastoma risk group and correlating this information with clinical phenotype (i.e., age, International Neuroblastoma Staging System stage, and International Neuroblastoma Pathology Classification); genetic factors (i.e., ploidy, MYCN status); and patient outcome.
OUTLINE: Tumor DNA samples are examined by mutation analysis for germline and somatic mutations in the ALK tyrosine kinase domain. Samples are analyzed by whole genome amplification using polymerase chain reaction and then sequenced for DNA alterations in the entire ALK coding sequence. Samples are also examined for single nucleotide polymorphisms (SNPs) by polymorphism analysis. Exploratory multivariable analysis is performed to test for the prognostic ability of ALK mutations in the presence of other known prognostic variables (i.e., age, International Neuroblastoma Staging System stage, MYCN status, International Neuroblastoma Pathology Classification, and diploidy).
A subset of tumor DNA samples from high-risk patients will be resequenced for DNA alterations to determine whether or not additional regions in ALK, outside of the tyrosine kinase domain, are prone to mutations and should be sequenced in a larger panel.
|Study Chair:||Yael P. Mosse, MD||Children's Hospital of Philadelphia|