The TARGET Osteosarcoma project elucidates comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of high-risk or hard-to-treat childhood cancers.
Osteosarcoma (OS) is the most common type of bone cancer in children and adolescents. It is most frequently diagnosed in adolescent patients experiencing periods of rapid growth. As with other childhood cancers being studied by TARGET, improvements in survival outcomes for OS have plateaued despite attempts in refining the standard treatment protocol. Additionally, patients endure rigorous therapy regimens regardless of whether the disease is localized or metastatic. Thus, targeted therapies have the potential to enhance the survival and quality-of-life of patients with this disease. To learn more about Osteosarcoma and current treatment strategies, visit the NCI osteosarcoma website.
As of September 1, 2019, the National Cancer Institute removed the restrictions limiting investigators from publishing broad results using osteosarcoma data from the TARGET initiative. OS datasets are available without restrictions on their use in publications or presentations.
TARGET investigators are analyzing tumors from pediatric patients to identify biomarkers that correlate with poor clinical outcome and/or new therapeutic approaches to treat childhood Osteosarcoma (OS). The tissues used in this study were collected from patients enrolled in Children's Oncology Group (COG) biology studies and clinical trials and through collaborations with The Hospital for Sick Children (SickKids) in Toronto (Ontario, Canada), Chiba Cancer Center (Chiba, Japan) and the Pediatric Oncology Institute in Sao Paolo, Brazil.
The OS project team members (like other TARGET researchers) are generating data in two phases: Discovery and Validation. Visit the TARGET Research page to learn more.
Discovery Dataset
The TARGET osteosarcoma (OS) project has produced comprehensive genomic profiles of ~90 clinically annotated patient cases within the discovery dataset. Each fully-characterized TARGET OS case includes data from nucleic acid samples extracted from tumor and normal tissues as follows:
- Primary tumor sample collected at the time of diagnosis
- Normal tissue sample from peripheral blood (case-matched)
Additional cases with partial molecular characterization and/or sequencing data are available to the research community.
Case Selection Criteria
Tissues and clinical data used for the TARGET OS project were obtained from patients enrolled on biology studies and clinical trials managed through the Children’s Oncology Group (COG) and through a collaboration with the Hospital for Sick Children (SickKids) in Toronto (Ontario, Canada). Patient samples with full characterization were chosen based on the following criteria:
- Tumor cellularity of >50% in tumor specimens and tumor necrosis of <50%
- High-quality nucleic acids in amounts adequate to complete comprehensive genomic profiling
Molecular Characterization
The TARGET OS project team relied on a variety of platforms to obtain a fully characterized dataset of ~90 cases. The COG OS Statistics and Data Center and personnel from Toronto SickKids provided clinical annotations and outcome data for all cases. Visit the TARGET Project Experimental Methods page for detailed information and protocols.
| General Methodology | Platform |
|---|---|
| Clinical Annotation | COG & SickKids Protocols |
| Gene Expression | Affymetrix U133 Plus 2.0 Array |
| Chomosome Copy Number Analyses & Loss of Heterozygosity | Affymetrix SNP 6.0 Array |
| Epigenetics (DNA Methylation) | Illumina Infinium 450K |
| miRNA Profiling | MegaPlex TaqMan Array |
| Whole Genome Sequencing | Complete Genomics Incorporated, Illumina Hi-Seq 2000 |
| Whole Exome Sequencing | Illumina Genome Analyzer II or Hi-Seq 2000 |
| mRNA-seq | Illumina Genome Analyzer IIx, Hi-Seq 2000 or Mi-Seq |
Verification of Discovery Variants
The TARGET OS project team utilized a variety of sequencing approaches to confirm candidate variants identified in the discovery sample cohort as somatic. For example, mRNA-seq results are being used to determine variants which were expressed and originally identified through whole genome or exome sequencing. These verified variants are being made available as open-access data (some initial results of integrated analysis of the TARGET Osteosarcoma discovery set based on whole genome and exome sequencing, custom targeted whole gene sequencing, mRNA-Seq and SNP array analysis are presented in the 
Oncoprint of Initial Integrated Analyses.pdf).
Validation Strategy
Some sequence mutations identified in the discovery cohort, along with some previously published variants, are being further analyzed in more than 180 additional cases. This validation effort is being performed in an unbiased cohort that was randomly selected based on tissue availability from patients enrolled on COG protocols and/or studies run through additional collaborative efforts (including international cohorts from Canada, Japan and Brazil), which allows for determination of the frequency of these changes across a broader spectrum of OS subtypes.
All data from the discovery and validation efforts are made available as specified in the Using TARGET Data and TARGET Publication Guidelines pages. The TARGET Data Matrix provides an overview of the data generated and described above.
The TARGET OS Project team consists of COG investigators at various institutions who work together with the scientists, analysts, project managers and technicians from the COG (Biorepository, Data and Statistics Core) and NCI offices (Office of Cancer Genomics, Clinical Therapy Evaluation Program, Center for Cancer Research and Center for Bioinformatics and Information Technology). This collaborative network is led by the following:
Principal Investigators
- Ching Lau, M.D., Ph.D.
- Jackson Laboratories (formerly Texas Children's Hospital)
- Paul Meltzer, M.D., Ph.D.
- National Cancer Institute, Center for Cancer Research
Scientific Investigators/Collaborators
- Timothy J. Triche, M.D., Ph.D.
- Children's Hospital of Los Angeles
- Irene Andrulis, Ph.D.
- Toronto SickKids, Canada
- Shintaro Iwata, M.D., Ph.D.
- Chiba Cancer Center, Japan
- Silvia Regina Caminada de Toledo
- GRAACC, Sao Paulo, Brazil