Trial Information

Neuroblastoma Biology Studies

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.