Biomarkers in Young Patients With Neuroblastoma

Completed

• Conditions: Neuroblastoma

• Registration Number: NCT01169376
• Lead Sponsor: Children's Oncology Group

Brief 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.

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-07-23
• Study First Submitted QC: 2010-07-23
• Study First Posted: 2010-07-26
• Status Verified: 2016-05
• Primary Completion: 2016-05
• Study Completion: 2016-05
• Last Update Submitted: 2016-05-17
• Last Update Posted: 2016-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 380

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Discovery of therapeutically relevant driver mutations

Secondary Outcome Measures

Name	Time	Method
Genome-wide DNA copy number and allelic status
Identification of a set of neuroblastoma specimens for analyses
Genome-wide methylation profile
Genome-wide microRNA expression profile
Genome-wide RNA expression signatures
Identification of mutations in candidate therapeutic targets
Characterization of the relapsed high-risk neuroblastoma genome and epigenome