Patient case: 4-year-old female with neuroblastoma; genetic feature: ALK

Clinical trial: Biomarkers in Young Patients With Neuroblastoma

Summary: RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.
  PURPOSE: This research study is studying biomarkers in young patients with neuroblastoma.

Detailed description: OBJECTIVES:
  Primary
  -  To discover the therapeutically relevant driver mutations in high-risk pediatric neuroblastoma.
  Secondary
  -  To identify a set of highly annotated neuroblastoma specimens (primary tumors and cell lines) for comprehensive genomic analyses, validation studies, resequencing efforts, and future functional assays.
  -  To define genome-wide DNA copy number and allelic status in at least 300 high-risk and 50 low-risk neuroblastoma primary untreated tumors, and 30 human neuroblastoma-derived cell lines.
  -  To define the genome-wide methylation profile of neuroblastoma in a minimum of 200 high-risk cases.
  -  To define the genome-wide microRNA expression profile of neuroblastoma in a minimum of 200 high-risk cases.
  -  To define genome-wide RNA expression signatures, including splice variations, in the same tumors and cell lines studied above.
  -  To identify mutations in candidate therapeutic targets using a staged resequencing strategy with ultimate genome-scale next generation resequencing of 3 genomes for 200 high-risk cases: the neuroblastoma genome and transcriptome as well as the paired constitutional genome.
  -  To characterize the relapsed high-risk neuroblastoma genome and epigenome.
  OUTLINE: This is a multicenter study.
  Previously collected samples are analyzed to define the genome-wide DNA copy number and allelic status; to define the genome-wide methylation profile of high-risk neuroblastoma cases; to define the genome-wide microRNA expression profile of high-risk neuroblastoma cases; to define the genome-wide RNA expression and relating gene expression to DNA copy number and gene polymorphisms, DNA methylation, and microRNA expression; to resequence three genomes: the neuroblastoma genome, the transcriptome, and the paired constitutional genome; and to characterize the relapsed high-risk neuroblastoma genome and epigenome.
  PROJECTED ACCRUAL: A total of 300 tumor samples from patients with high-risk disease, 50 tumor samples from patients with low-risk primary neuroblastoma, and 30 human neuroblastoma-derived cell lines will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Registered on the COG-ANBL00B1 Neuroblastoma Biology Study or its CCG or POG precursor
  -  Sufficient high-quality tumor material available for the proposed studies meeting the following criteria:
  -  Tissue histopathologic review with > 70% tumor cells in sections adjacent to areas used for nucleic acid preparation
  -  Matched normal cells (blood or uninvolved bone marrow) available
  -  ≥ 5 μg DNA available
  -  ≥ 5 μg RNA available
  -  ≥ 200 mg tissue available
  -  Tumor samples must meet 1 of the following criteria:
  -  High-risk tumor
  -  With or without MYCN amplification
  -  With or without tumor progression or relapse (during ≥ 2.5 years of follow up)
  -  Patients aged 18 months to 5 years
  -  Low-risk tumor
  -  Primary neuroblastoma
  -  Stage I disease (completely resected)
  -  No event in ≥ 3 years of follow up
  -  Cell lines representing diverse high-risk genetics including with or without MYCN amplification and clinical course (at diagnosis or after relapse)
  PATIENT CHARACTERISTICS:
  -  Not specified
  PRIOR CONCURRENT THERAPY:
  -  Not specified

Relevance to patient case: not relevant