The Pediatric Cancer Genome Project: Era of Discovery

St. Jude and Washington University launch the Pediatric Cancer Genome Project (PCGP). Scientists will ultimately compare the complete genomes of both cancerous and normal cells of about 800 children with some of the toughest and least understood pediatric cancers. Most of the tissue samples come from the St. Jude Biorepository, which was created in the 1970s to store biological samples for research.

The amount of data generated by the PCGP is staggering: For every patient, scientists sequence the 3 billion base pairs of the child’s normal genome and the 3 billion base pairs of the child’s cancer genome. St. Jude researchers push to create data mining tools to maximize discoveries, including a computer tool called CREST. This new system outperforms prior tools so well that it is adopted by scientists worldwide.

PCGP leaders announce the largest-ever release of comprehensive human cancer genome data for free access by the global scientific community. The amount of information released more than doubles the volume of high-coverage, whole-genome data available from all human genome sources combined.

TIME magazine names the PCGP to its list of top 10 medical breakthroughs.

Researchers begin to publish discoveries gleaned from the PCGP. The project will yield groundbreaking findings regarding brain tumors, leukemia, solid tumors and a neurodegenerative disorder known as Lou Gehrig’s disease. The findings will pinpoint mutations never before linked to cancer, identify subtype-specific mutations, define novel cancer subtypes, highlight how cancer develops and reveal changes that affect how cells “read” genes.

St. Jude and the Howard Hughes Medical Institute collaborate to create the Childhood Solid Tumor Network. This service was launched to fuel research by providing preclinical resources to scientists worldwide. That network and PROPEL, offered in 2018 as one of the world’s largest collections of leukemia samples, will accelerate global progress toward understanding and treating pediatric cancer.

The hospital embarks on the second phase of the PCGP, which takes genomic medicine to the next level. Phase II includes digging deeper into the genomic makeup of pediatric cancers. This phase also signals a new era of clinical genomics as St. Jude moves toward comprehensive genomic testing for all eligible patients.

Success of the PCGP sparks creation of the St. Jude Cancer Predisposition Program for children and families who may have inherited genetic mutations that leave them at higher-than-normal risk of cancer.

The PCGP reports that a surprisingly high percentage — nearly 1 in 10 — of childhood cancer patients carry germline (inherited) mutations in known cancer predisposition genes.

St. Jude announces development of ProteinPaint and CONSERTING, the first of more than a half dozen data analysis and visualization tools. These free tools allow researchers worldwide to access and evaluate PCGP data. 

The hospital opens the TOTAL 17 clinical trial for children with leukemia and lymphoma. This is one of several studies that reflect insights gained from the PCGP. The PCGP findings are also incorporated into other clinical trials at St. Jude and internationally that aim to improve cure rates for children with medulloblastoma, diffuse intrinsic pontine glioma and other cancers.

St. Jude launches St. Jude Cloud, an online data-sharing and collaboration platform that provides researchers access to the world’s largest public repository of pediatric cancer genomics data. The project is a partnership among St. Jude, DNAnexus and Microsoft.

In the largest comprehensive genomic analysis yet of neuroblastoma, scientists dramatically increase our knowledge about how many mutations drive the cancer’s growth and spread. Researchers also show how a common mutation may fuel this cancer. The findings highlight possible strategies for precision medicine.

St. Jude scientists create orthotopic patient-derived xenograft models representing a variety of pediatric brain tumor types. These molecularly characterized models are available through a cloud-based data portal.

St. Jude scientists have published more than 35 articles in peer-reviewed journals outlining discoveries that originated with the PCGP. Publications continue to appear and have included the New England Journal of Medicine, Nature and other prestigious journals.

From Promise, Special Edition 2020