Understanding the biology of many childhood cancers, while expanding, remains in many instances insufficient for the development of novel treatments for these young patients. Pan-cancer model systems, including cell lines and xenografts, have been applied in basic research to expand the knowledge of cancer mechanisms and treatment response. These model systems have been limited for pediatric cancers; however, an increasing number are becoming available to the research community for use at the bench and in the clinic. As a result, the TARGET Pan-cancer Model Systems (MDLS) were developed to study the mechanisms of tumor development and response to treatments of high-risk or hard-to-treat childhood cancers.
In the TARGET initiative, some disease projects characterized tumor cell lines or xenografts, with or without matched normal comparators, as well as some non-cancerous tissues from the same organ. TARGET and other programs added value to the cell lines and patient-derived xenograft (PDX) models by sequencing their DNA and/or RNA. These reagents are available for in vitro validation experiments, and their molecular characteristics are available through the TARGET Data Matrix.
MDLS includes acute leukemia cell lines and xenografts with matched primary and/or relapsed tumor information, neuroblastoma cell lines and xenografts with matched controls, kidney tumor cell lines, normal brain tissues, and embryonic stem cell lines that were sequenced for some TARGET disease projects. Additionally, TARGET has provided whole exome sequencing for 131 cell lines and xenografts from the NCI’s Pediatric Preclinical Testing Program; many of these have associated expression and copy number data available through the TARGET Data Matrix as well.
The following links are for cell line data that have been moved to the TARGET-MDLS project:
Rhabdoid Tumor and Embryonic Stem Cells
- Bisulfite Sequencing
- ChIP Sequencing
- miRNA Sequencing
- mRNA Sequencing
- Whole Genome Sequencing
Pediatric Preclinical Testing Program
- Clinical
- Copy Number Array
- Gene Expression Array
- Miscellaneous
- Sample Matrix
- Whole Exome Sequencing
Neuroblastoma
- Clinical
- Sample Matrix
- Whole Genome Sequencing
- https://target-data.nci.nih.gov/Public/MDLS/NBL/WGS/CGI/READMEs/
- https://target-data.nci.nih.gov/Public/MDLS/NBL/WGS/L3/copy_number/CGI/
- https://target-data.nci.nih.gov/Public/MDLS/NBL/WGS/L4/circos/CGI/
- https://target-data.nci.nih.gov/Public/MDLS/NBL/WGS/METADATA/
- https://app.globus.org/file-manager?origin_id=08ab5ada-d3df-11e9-939f-02ff96a5aa76&origin_path=%2FMDLS%2FNBL%2FWGS%2FL3%2F
- https://app.globus.org/file-manager?origin_id=08ab5ada-d3df-11e9-939f-02ff96a5aa76&origin_path=%2FMDLS%2FNBL%2FWGS%2FCGI%2F
- Whole Exome Sequencing
The NCI-supported Pediatric Preclinical Testing Program (PPTP) was a comprehensive program to systematically evaluate new agents against molecularly characterized childhood solid tumor and leukemia models. The primary goal of the PPTP was to identify new agents that have the potential for significant activity when clinically evaluated against selected childhood cancers. The program was based on a substantial body of data showing that appropriate childhood cancer preclinical in vivo models could recapitulate the antitumor activity of known effective agents and prospectively identify novel agents subsequently shown to have clinical activity against specific cancers of children and adolescents.
The Pediatric Preclinical Testing Consortium (PPTC) is designed to produce reliable preclinical in vivo data using genomically characterized PDX lines so that childhood cancer clinical researchers can better prioritize which agents to pursue in pediatric clinical trials. PPTC, previously known as PPTP, has developed over 370 PDX models from high-risk childhood cancers. Effective prioritization of truly active agents for pediatric clinical testing is essential to future success in identifying more effective treatments for children with cancer.
The PPTC RNA Sequencing and Whole Exome Sequencing data are available via the Sequence Read Archive (SRA) Run Selector at https://trace.ncbi.nlm.nih.gov/Traces/study/?acc=phs001437.
Nomenclature Issue to Note Within the PPTC Dataset
After release of the PPTC dataset, cases “TARGET-80-PPT045” and “TARGET-80-PPT046” were determined to be the same individual where all samples associated with the TARGET-80-PPT045 case barcode are diagnosis samples and those associated with the TARGET-80-PPT046 barcode are relapse samples. Since this determination was not made until after release, some sample barcodes do not accurately reflect the correct sample type codes for this case.
Specifically, both TARGET-80-PPT046-60A-99R and TARGET-80-PPT046-60A-01D are relapse Xenograft samples, but they were originally assigned the “60” sample type code which is for primary Xenograft samples. Therefore, the tissue codes for these two samples are incorrect.
The MDLS project team includes the PPTP Principal Investigator (PI) from Greehey Children’s Cancer Research Institute, PPTC PI from The Children’s Hospital of Philadelphia, Children’s Oncology Group (COG) investigators from various institutions, and National Cancer Institute (NCI) staff. The MDLS project team works with the scientists, analysts, project managers, and technicians from the COG (Biorepository, Data, and Statistics Core) and NCI offices (Office of Cancer Genomics, Cancer Therapy Evaluation Program, Center for Cancer Research, and Center for Bioinformatics and Information Technology). This collaborative network is led by:
Program Director
-
Malcolm Smith, Ph.D.
- National Cancer Institute, Cancer Therapy Evaluation Program
PPTP Principal Investigator
- Peter Houghton, Ph.D.
- Greehey Children’s Cancer Research Institute
PPTC Principal Investigator
- John M. Maris, MD
- The Children’s Hospital of Philadelphia
- Rokita JL, Rathi KS, Cardenas MF, et al. Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design. Cell Rep. 2019 Nov 5;29(6):1675-1689.e9. (PMID: 31693904) View PubMed abstract