Predicting Outcome for Patients with Metastatic Neuroblastoma by Analysis of Bone Marrow and Blood for a Neuroblastoma Gene Expression Signature

Neuroblastoma develops in the nervous system outside the brain and already has spread at diagnosis, especially to bone marrow, in 50% of patients. It is the most common solid tumor in children after brain tumors.  PROBLEM.  Although treatment has improved for patients with widespread, high-risk disease, only 45% survive long-term.  Failure frequently occurs because tumor cells survive and grow in bone marrow. Currently, a test is not available to accurately measure a wide range of tumor cells (100% - 0.0001%) in bone marrow and blood at diagnosis and during and after therapy.  ATTACKING THE PROBLEM.  The proposed research will determine if a new molecular test that we have developed to measure expression of five genes that are active in neuroblastoma but not normal bone marrow or blood cells improves our ability to use bone marrow or blood samples to evaluate response and predict outcome.  This test, which can identify one neuroblastoma cell among 1,000,000 normal marrow or blood cells (0.0001%), will be used to assess 660 bone marrow and 100 blood specimens from children with high-risk, widespread neuroblastoma.   IMPORTANCE OF RESEARCH. Based upon results that we already have obtained, we anticipate that this test will provide a major improvement in our ability to evaluate response of high-risk neuroblastoma to treatment and so will provide an early surrogate of the ultimate success of treatment.  This new 'gold standard' test for tumor cells in bone marrow and blood will be an important biomarker assay for evaluating new treatments for widespread, high-risk neuroblastoma.