Biomarkers in Young Patients With Neuroblastoma

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.

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 Criteria:
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