OCG Data Coordinating Center

Leidos Biomedical Research, Inc., Frederick MD

Investigators

Abstract

This proposal proposes to continue operations and maintenance of the OCG (ocg.cancer.gov) Data Coordinating Center (DCC) to accept, QC, and display data and data types generated by the TARGET, CGCI, CTD2 and other cancer genomics and translation projects. The primary focus of the TARGET and CGCI Initiatives remain identifying genomic alterations that offer pathways to novel therapeutic interventions that may lead to more effective treatments for cancers. NCI-CBIIT provides informatics support for the OCG programs. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative focuses to rapidly identify potential therapeutic targets in childhood cancers so that new, more effective treatments can be developed in shorter time and ultimately bring new hope to children and their families who face the devastating burden of these diseases. The TARGET Initiative (is focused on identifying therapeutic targets as well as prognostic and diagnostic markers in multiple childhood cancers. The initiative includes the study of high-risk Acute Lymphoblastic Leukemia (ALL), neuroblastoma (NBL), high-risk and treatment refractory Acute Myeloid Leukemia (AML), osteosarcoma (OS), and kidney tumors (including high risk Wilms tumor). These cancers were the chosen for study because of their prevalence among children, the inadequacy of current treatment options, the ongoing NCI-supported efforts to molecularly characterize these cancers, and the availability of clinically annotated, high-quality human tissue collections that met TARGET's strict scientific, technical, and ethical requirements. In the coming year, TARGET will include validation cohorts and other studies. The Cancer Genome Characterization Initiative (CGCI) supports cutting-edge genomics research on rare cancers. Researchers develop and apply advanced sequencing and other genome-based methods to identify novel genetic abnormalities in tumors. The extensive genetic profiles generated by CGCI may inform better cancer diagnosis and treatment. CGCI is another OCG program. CGCI focuses Burkitt Lymphoma and HIV+ Tumor Molecular Characterization Project (HTMCP). Previous projects included early stage Lung Cancers, Medulloblastoma, and Non-Hodgkin Lymphoma. The goal of the Burkitt Lymphoma Genome Sequencing Project (BLGSP) is to explore potential genetic changes in patients with Burkitt lymphoma that could lead to better prevention, detection, and treatment of this rare and aggressive cancer. The OCG, along with the Office of HIV and AIDS Malignancies (OHAM), initiated the HTMCP to gain insight into the genetic events driving HIV-associated cancers and to determine why certain cancers, but not others, have higher incidences in HIV-positive patients. The data generated by these projects are stored at the DCC. Cancer Target Discovery and Development (CTD²) initiative bridges the gap between the enormous volumes of data generated by genomic characterization studies and the ability to use these data for the development of human cancer therapeutics. It specializes in computational and functional genomics approaches critical for translating next-generation sequencing data. The Cancer Target Discovery and Development (CTD2) initiative is a collaborative network of OCG-supported Centers. The program strives to functionally validate discoveries from large-scale genomic initiatives and advance them toward precision medicine through the efforts of the Centers and open access data sharing. Through cross-Network collaborations, CTD2 uses innovative bioinformatics and functional biology to: (1) mine data to find alterations that potentially influence tumor biology, (2) characterize the functional roles of candidate alterations in cancers, and (3) identify novel approaches that target causative alterations either directly or indirectly. Because CTD2 is a ?community resource project all information in the Data Portal is openly available to the scientific community and can be accessed without restrictions. Project descriptions, datasets, and methodologies generated by the Centers are shared through the CTD2 Data Portal (i.e. the OCG Data Coordinating Center). OCG oversees other genomics and translation projects which may generate molecular data that will be stored in the DCC. The formats, file types etc. is ever changing and the DCC evolves as needed. It is expected that the infrastructure already developed and being developed will be useable for the OCG data generated. The research conducted by OCG programs is divided into three distinct yet tightly integrated components that together form a system for selecting new molecular targets for the development of novel therapies for these childhood cancers: ? Genomic Characterization: Using high-resolution array-based methods a)determine differences in the patterns of gene expression in cancer samples and non-cancerous samples and b) genome changes to characterize genome structural changes that correlate with each cancer, such as chromosome region gains and losses, methylation changes etc. are integrated to provide a complete genomic overview of each cancer. ? Sequencing: Up-to-date genetic sequencing techniques are used to read genes that have been identified to have altered expression and/or structural alterations to identify the specific cancer-related mutations in the DNA sequence. Additionally, new technologies to sequence the whole-genome, whole-exome, RNA-seq, and miRNA-seq have and will be employed. ? Identification of Therapeutic Targets?For example, RNA interference (RNAi), small molecule high-throughput screens are used to identify and initially validate potential targets identified from the genomic characterization and re-sequencing efforts. In the future, other approaches may be added.