Studying Biomarkers in Samples From Patients With High-Risk Neuroblastoma

Study Overview
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Brief Summary
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RATIONALE: Studying samples of blood and tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. PURPOSE: This research trial studies biomarkers in samples from patients with high-risk neuroblastoma.

Detailed Description
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OBJECTIVES: To establish telomere length measurement by quantitative polymerase chain reaction (qPCR) as an alternative lengthening of telomeres (ALT) detection method in neuroblastoma (NB). To determine the frequency of ALT in high-risk NB and the characteristics of ALT+ NB. To establish C-circle (extra-chromosomal telomeric DNA circles) level as a marker of ALT activity in NB. To evaluate the prognostic significance of ALT in NB. To evaluate the utility of the C-circle assay for the detection of circulating tumor DNA in NB patients with an ALT+ tumor. OUTLINE: Archived tumor tissue and serum samples are analyzed for telomere length measurement, frequency, and C-circle levels by PCR. Results are then compared with patients' age at diagnosis and outcomes including survival data (event-free and overall survival).

Official Title
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Alternative Lengthening of Telomeres (ALT) in Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Genetic: DNA analysis
* Genetic: polymerase chain reaction
* Other: laboratory biomarker analysis
* Other: medical chart review


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Snap-frozen neuroblastoma (NB) tumors collected at diagnosis (Objectives 1 to 3) High-risk stage 3 or 4 NB AND MYCN non-amplified, i.e., exclude stage 4 infants who are not high-risk Up to five high-risk (> 18 months, unfavorable histology) stage 3/MYCN non-amplified tumors Patients preferably treated on protocol COG-A3973 or similar protocols with myeloablative therapy At least 3 years of follow-up for those with no event (current evidence suggests that ALT+ NBs often relapse late, i.e., 2 years or longer from diagnosis) NB tumor DNA collected at diagnosis (Objectives 2 & 3) High-risk stage 3 or 4 NB as for Objective 1, except for MYCN status Stage 4 tumors are preferred; may include up to seven high-risk stage 3 tumors with similar distribution of MYCN-amplified and non-amplified tumors Frozen serum from NB patients (Objective 5; 2nd stage of project) Paired serum obtained at diagnosis from patients with ALT+ or ALT- tumors identified in Objective 2 PATIENT CHARACTERISTICS: Not specified PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: DNA analysis|nan|
|Genetic: polymerase chain reaction|nan|
|Other: laboratory biomarker analysis|nan|
|Other: medical chart review|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The sensitivity and specificity, as well as the optimal cut-off, for telomere length (TL) qPCR as an ALT detection method |  |  | 
| Frequency and characteristics of ALT in high-risk NB |  |  | 
| C-circle level as a marker of ALT activity in NB |  |  | 
| Prognostic value of ALT |  |  | 
| C-circle assay utility in detecting tumor DNA in the serum of NB patients with an ALT |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage 4S neuroblastoma, localized resectable neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma