Abstract 4869: The Signature Study: Molecular analysis of pediatric tumors with establishment of tumor models in a biology study
Authors: VanSickle Elizabeth , Zhao Ping , Mitchell Deanna , Foley Jessica , Steinbrecher Julie , Rich Maria , Nagulapally Abhinav , Bond Jeff , Hendricks William , Sholler Giselle Saulnier 
Published: July 2017

Background: Pediatric cancer is the leading cause of death by disease in children in the US. Significant advances have been made in survival in the past 30 years and genomic understanding of tumors is underway. Gains in the identification of biomarkers, drug targets, and the molecular characterization of cancer are due to improved technology including gene sequencing, proteomics, and epigenetics. Still, this remains limited primarily to large academic centers and patients with high risk/metastatic disease experience &lt; 30% survival. Phase 1/2 trials not based on precision medicine result in poor response rates (&lt;10%). Therefore, genomic understanding of tumors and molecular targeted therapies with aims of reaching all children and reducing toxicity while improving efficacy is needed.

Methods: The Signature Study is an IRB-approved biology study that seeks to perform genomic analysis, high throughput (HTP) drug testing, and creation of patient derived xenograft (PDX) models of all pediatric cancer patients diagnosed/relapsed at Helen DeVos Children’s Hospital. Patients are consented, clinical history is collected in RedCap, and tumors are collected flash frozen and in cell culture media. Blood is collected for germline analysis. Tumors are analyzed through gene expression arrays, DNA panels and exomes and RNA sequencing. Tumors in cell culture are used for generation of primary patient cell lines (confirmed by IHC and STR) and immediate injection into NSG mice for PDX models. Cell lines undergo HTP drug testing using the Prestwick and NCI drug libraries, novel therapeutics and combinations.

Results: Enrollment has increased since inception in 2011 with now &gt;50 patients/year; a total of 284 pediatric tumors collected representing over 30 tumor types. The most common diagnosis is neuroblastoma, followed by medulloblastoma, osteosarcoma, and rhabdomyosarcoma. Sequencing for genomic analysis has been performed on 166 tumors to identify mutations, fusions, CNV, and deletions. To date 184 have been grown as primary patient cell lines and 75 as PDX models. Over 60 samples have been evaluated in HTP drug testing. Genomic analysis of cultured tumor cells has been correlated with response to drug libraries to establish correlative predictive markers for therapeutic decision making to be tested in clinical trials. The study stores remaining tissue, cell lines, and PDX models for additional future research. Conclusion: This study shows it is feasible for a mid-sized hospital system to coordinate and collect tumors for genomic analysis in real time for clinical decision making in the future. This resource is an integrated TransMed database system which is a powerful resource which correlates clinical outcomes, therapies, genomic sequencing, PDX models and HTP drug testing used to answer research questions of biomarkers, biological characterization, drug sensitivity, and driver pathways within and between pediatric cancers.

Citation Format: Elizabeth VanSickle, Ping Zhao, Deanna Mitchell, Jessica Foley, Julie Steinbrecher, Maria Rich, Abhinav Nagulapally, Jeff Bond, William Hendricks, Giselle Saulnier Sholler. The Signature Study: Molecular analysis of pediatric tumors with establishment of tumor models in a biology study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4869. doi:10.1158/1538-7445.AM2017-4869