THE CHILDRENS HOSPITAL LOS ANGELES

Although treatment has steadily improved in the past 20 years for children with high-risk metastatic neuroblastoma (stage 4), only 40% of these patients survive long-term. Our overall goal is to improve survival for these children. Problem: It is not possible at diagnosis to predict which patients will be long-term progression-free survivors (PFS) and which will succumb to disease. This is necessary in order to develop improved, risk stratified therapies. Hypothesis: Molecular “signatures” that are derived from microarray analyses of tumor RNA and DNA will define subgroups that have either excellent or poor outcomes. Specific aims: 1) To further improve our current molecular signatures for predicting PFS by using higher resolution microarray RNA expression profiling; and 2) To translate new and improved microarray molecular signatures into clinically applicable TaqMan® Low Density Array (TLDA) assays for use in 2011. Summary: We have discovered that molecular signatures of both tumor cells and their microenvironment can contribute to clinically applicable classification of tumors. These are the first and currently only studies aimed at defining subgroups among clinically defined high-risk stage 4 patients. Prediction of long-term PFS using molecular classification will facilitate assignment of treatment and development of more effective therapy. We aim to have a molecular classifier available for clinical implementation in 2011. We have generated large amounts of data from RNA (Affymetrix U133A and U133B, Human Exon) and DNA (Affymetrix 6.0 SNP) microarrays and from TLDA assays. This Administrative Supplement will fund a full-time bioinformatician with skills in databases, algorithms, and computational and statistical techniques to help manage our data and to participate in its analysis. Such a person will significantly increase our progress by further enhancing the biostatistics/bioinformatics strength of our research. This Administrative Supplement will allow us to increase the tempo of our research so that we shall reach our goal of clinical implementation of a nationwide reference laboratory for molecular classification of high-risk neuroblastoma in 2011. Specifically, the Administrative Supplement to this R01 will allow us to accomplish the following goals of the ARRA: 1. It will increase the tempo of scientific research of our R01 that is in line with our original peer-reviewed and approved objectives. 2. It will create one new, full-time job for a relatively new graduate with a Master’s Degree in biostatistics or bioinformatics. 3. It will speed the development of clinically applicable risk assessment so that such testing can be incorporated into nationwide clinical trials for children with high-risk neuroblastoma by the Children’s Oncology Group in 2011. It will provide us the biostatistics and bionformatic capacity to perform risk assessment for these studies, which enroll approximately 200 patients annually. 4. It will enable us to purchase equipment that can be dedicated to testing of specimens from patients in a CAP/CLIA laboratory, which is necessary for integration into clinical trials. This reference laboratory will benefit all institutions in North America treating children with high-risk neuroblastoma.

Clarification of Codes