Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma

• Factors currently used for risk-group assignment (DNA content, MYCN copy number, and tumor histology) [ Designated as safety issue: No ]
• Prevalence of 1p, 11q, 14q loss of heterozygosity and gain of 17q [ Designated as safety issue: No ]
• Expression of nerve growth factor and its high affinity (Trk-A) and low affinity (p75NTR) receptors [ Designated as safety issue: No ]
• Telomerase activity [ Designated as safety issue: No ]
• Comparison of the independent clinical significance of biological factors with MYCN amplification, International Neuroblastoma Staging system stage, age, and histologic variables in predicting response to treatment or outcome [ Designated as safety issue: No ]

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 laboratory study is looking at biomarkers in tumor tissue samples from patients with newly diagnosed neuroblastoma or ganglioneuroblastoma.

OBJECTIVES:

• Evaluate the factors currently used for risk-group assignment (DNA content, MYCN copy number, and tumor histology) in patients with newly diagnosed neuroblastoma or ganglioneuroblastoma.
• Assess the prevalence of 1p, 11q, 14q loss of heterozygosity and gain of 17q; the expression of nerve growth factor and its high affinity (Trk-A) and low affinity (p75^NTR) receptors; and telomerase activity in these patients.
• Compare the independent clinical significance of these biological factors with MYCN amplification, International Neuroblastoma Staging system stage, age, and histologic variables in predicting response to treatment or outcome in these patients.
• To prospectively analyze the concordance between detection of MYCN amplification in tumor samples and quantitative detection of MYCN DNA in serum, and to analyze the prognostic significance of MYCN amplification as detected in serum samples.
• To build a database that includes information regarding the presentation and natural history of neuroblastoma-associated health problems including, but not limited to, opsoclonus myoclonus ataxia (OMA) and/or spinal cord compression.
• Maintain a reference bank containing clinically and genetically characterized frozen tumor tissue, tumor DNA and RNA, tumor touch preparations, histology slides and blocks, cell lines, and paired normal DNA obtained at time of diagnosis, second-look surgery, and relapse for future research studies.
• Build a database of known biological prognostic factors for patients on therapeutic studies.

OUTLINE: This is a multicenter study. Patients are stratified according to International Neuroblastoma Staging System stage (stage 1 vs stage 2A vs stage 2B vs stage 3 vs stage 4 vs stage 4S) and age (under 365 days vs 365 days and over).

Tumor samples are obtained at the time of surgery (diagnosis). Tumor samples may also be obtained at the time of second-look surgery and/or relapse. Blood and bone marrow samples are also obtained.

MYCN copy number is analyzed by fluorescent in situ hybridization (FISH). Tumor cell ploidy is determined by flow cytometric analysis. Allelic status of 1p36, 11q23, and 14q32 is determined by multiplexed fluorescence polymerase chain reaction (PCR). Real-time quantitative PCR and FISH are used to determine 17q gain. Neurotrophin and neurotrophin receptor expression and the level of telomerase RNA expression is determined by reverse transcription-PCR. Telomerase activity is assessed by a telomeric repeat amplification protocol assay in patients with stage 2 or 4S disease.

Patients are followed within 2 weeks and then annually (if not on a concurrent therapeutic study).

PROJECTED ACCRUAL: Approximately 10,000 patients will be accrued for this study within 6 years.

• Genetic: fluorescence in situ hybridization
• Genetic: gene expression analysis
• Genetic: nucleic acid amplification
• Genetic: polymerase chain reaction
• Genetic: reverse transcriptase-polymerase chain reaction
• Other: cytology specimen collection procedure
• Other: flow cytometry
• Procedure: biopsy

• Henderson TO, Bhatia S, Pinto N, London WB, McGrady P, Crotty C, Sun CL, Cohn SL. Racial and Ethnic Disparities in Risk and Survival in Children With Neuroblastoma: A Children's Oncology Group Study. J Clin Oncol. 2011 Jan 1;29(1):76-82. Epub 2010 Nov 22.
• Cohn SL, Bhatia S, London WB, et al.: Racial and ethnic disparities in disease presentation and survival among children with neuroblastoma (NBL): A Children's Oncology Group (COG) study. [Abstract] J Clin Oncol 28 (Suppl 15): A-9517, 2010.
• Moreau LA, McGrady P, London WB, Shimada H, Cohn SL, Maris JM, Diller L, Look AT, George RE. Does MYCN amplification manifested as homogeneously staining regions at diagnosis predict a worse outcome in children with neuroblastoma? A Children's Oncology Group study. Clin Cancer Res. 2006 Oct 1;12(19):5693-7.

DISEASE CHARACTERISTICS:

• Diagnosis of neuroblastoma or ganglioneuroblastoma within the past two weeks

  • Patients with relapsed neuroblastoma who were not enrolled on ANBL00B1 at original diagnosis are NOT eligible
• No prior enrollment on a front-line COG therapeutic study (low-, intermediate-, or high-risk)

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• Not specified