Date Published: July 21, 2017
Publisher: Public Library of Science
Author(s): Jason Glover, Tsz-Kwong Man, Donald A. Barkauskas, David Hall, Tanya Tello, Mary Beth Sullivan, Richard Gorlick, Katherine Janeway, Holcombe Grier, Ching Lau, Jeffrey A. Toretsky, Scott C. Borinstein, Chand Khanna, Timothy M. Fan, Dominique Heymann.
The prospective banking of osteosarcoma tissue samples to promote research endeavors has been realized through the establishment of a nationally centralized biospecimen repository, the Children’s Oncology Group (COG) biospecimen bank located at the Biopathology Center (BPC)/Nationwide Children’s Hospital in Columbus, Ohio. Although the physical inventory of osteosarcoma biospecimens is substantive (>15,000 sample specimens), the nature of these resources remains exhaustible. Despite judicious allocation of these high-value biospecimens for conducting sarcoma-related research, a deeper understanding of osteosarcoma biology, in particular metastases, remains unrealized. In addition the identification and development of novel diagnostics and effective therapeutics remain elusive. The QuadW-COG Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) has developed the High Dimensional Data (HDD) platform to complement the existing physical inventory and to promote in silico hypothesis testing in sarcoma biology. The HDD is a relational biologic database derived from matched osteosarcoma biospecimens in which diverse experimental readouts have been generated and digitally deposited. As proof-of-concept, we demonstrate that the HDD platform can be utilized to address previously unrealized biologic questions though the systematic juxtaposition of diverse datasets derived from shared biospecimens. The continued population of the HDD platform with high-value, high-throughput and mineable datasets allows a shared and reusable resource for researchers, both experimentalists and bioinformatics investigators, to propose and answer questions in silico that advance our understanding of osteosarcoma biology.
Osteosarcoma is a cancer of the bone that is most common in the pediatric and young adult population . The therapeutic management of osteosarcoma has not substantively changed since the introduction of systemic chemotherapy in the 1980’s, and consequently survival rates for osteosarcoma have remained largely static for the past 3 decades. In a minority, yet substantive percent of patients (~30%), cure remains unachievable given the development of recurrent or metastatic disease . For these high risk patients, there is strong clinical and scientific impetus for increasing the fundamental understanding of osteosarcoma biology, in particular the cellular mechanisms of metastases. The ultimate goal shared by clinicians and scientists would be the identification and development of rational treatment options for osteosarcoma patients at high risk for disease relapse or progression.
Relational biological databases can serve as powerful and reusable discovery tools for deepening the understanding of complex and interactive processes, such as cancer biology. Gleaning from collected scientific experiments, published investigative studies, and high-throughput experimental technologies, biological databases have the capacity to act as digital warehouses of information. These databases can be organized in varying combinatorial matrices to test preliminary hypotheses with the consequent acceleration of new exploratory questions that validate the merit of additional focused research.
The HDD platform serves as a relational database resource to facilitate discoveries relevant to sarcoma biology, and serves as an investigative resource available to the sarcoma research community. To utilize current datasets stored within the HDD platform, researchers should contact the QuadW-COG Childhood Sarcoma Biology and Annotation Office through firstname.lastname@example.org.