NCI Cancer Model Development
NCI-supported cancer model development is a collaborative effort, which includes model development centers and model processing entities that provide clinical data, quality control, biospecimen processing, and molecular characterization.
Map of the Cancer Model Development Centers (CMDCs) and model processing entities. The map shows locations of the CMDCs: Broad Institute in Cambridge, Massachusetts, USA; Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, USA, and their subsites: Hubrecht Institute in Utrecht, Netherlands and University of Verona in Verona, Italy; Biospecimen Processing Center at the Nationwide Children’s Hospital in Columbus, Ohio, USA; Genome Characterization Centers at Broad Institute in Cambridge, Massachusetts, USA, and University of North Carolina in Chapel Hill, North Carolina, USA; Genomic Data Commons in Chicago, Illinois, USA; and Clinical Data Coordinating Center at the Information Management Services in Rockville, Maryland, USA.
The Cancer Model Development Centers (CMDCs) are the NCI-funded contributors to the HCMI. CMDCs are tasked with producing next-generation cancer models from clinical samples. The cancer models include tumor types that are rare, originate from patients from underrepresented populations, lack precision therapy, or lack cancer model tools. Throughout the development process, the CMDCs utilize stringent internal quality control measures to ensure both clinical and molecular integrity. These models are then annotated with clinical and genomic data and are available as a community resource.
The two CMDCs are:
Broad Institute of Harvard and MIT (BROD): The BROD CMDC co-Directors are Jesse S. Boehm, Ph.D. and Keith L. Ligon, M.D., Ph.D.
Cold Spring Harbor Laboratory (CSHL): The Principal Investigator for the CSHL CMDC is David A. Tuveson, M.D., Ph.D. The CSHL CMDC includes two international subsites: 1) ARC-Net Centre for Applied Research on Cancer, University of Verona, co-led by Aldo Scarpa, M.D., Ph.D. and Vincenzo Corbo, Ph.D. and 2) Hubrecht Institute, led by Hans Clevers, M.D., Ph.D.
The HCMI CMDC-specific model development pipeline involves multiple institutions and includes several quality control check points which ensures that the models and associated clinical and molecular data are complete and consistent for researchers.
CMDC Simplified Flowchart. The models are first generated by the CMDCs and clinical data associated with the model is submitted to the CDC. The CDC quality controlled (QC’ed) clinical data for the model is sent to the GDC. Samples of normal tissue, parent tumor, and model are sent to the BPC for isolation of nucleic acids. The QC’ed nucleic acid samples are sent to the GCCs for WXS, WGS and RNA-Seq and raw sequencing data is submitted to the GDC. Additional QC data from the CMDCs and the BPC are sent to the DCC for storage. CMDC-validated models and their associated genomic and clinical data will be provided as an HCMI resource to the research community.
The clinical data is submitted to NCI-contracted Clinical Data Center (CDC) at Information Management Services, Inc. The CDC collects and quality controls (QCs) the clinical data to confirm patient privacy is protected and to certify that the submitted clinical data conforms to the controlled vocabulary of the case report forms (CRFs).
Nationwide Children’s Hospital (NCH) serves as the Biospecimen Processing Center (BPC) for the NCI CMDCs. DNA is isolated from normal tissue, parent tumor, and the derived model while RNA is isolated from the parent tumor and model using standardized protocols. Internal BPC quality control and genotyping ensure quality and consistency of material for molecular characterization.
The NCI-funded genomic characterization centers (GCCs) are:
- Broad Institute:15X whole genome sequencing (WGS) and 150X whole exome sequencing (WXS) are performed on DNA from normal tissue, parent tumor, and derived model.
- The University of North Carolina: RNA sequencing (RNA-Seq) of RNA from the parent tumor and the derived model are performed.
Sequencing data are submitted to NCI Genomic Data Commons (GDC) for storage and harmonization by their analytical pipeline. GDC also houses the quality-controlled clinical data.
All data will be made available in a way that protects patient privacy.
HCMI Searchable Catalog is a resource for querying the next-generation models developed by HCMI. Within the catalog, users will be able to search by patient demographics, tumor, and model elements. For example, searchable data elements include age at diagnosis, sex, treatment information, clinical tumor diagnosis, primary site, clinical stage, and type of model (e.g. 3D-organoid, 2D-conditionally reprogrammed cells), etc.