Pediatric Cancer Genome Project sparks a decade of discovery

With more than 3 billion base pairs of DNA, the human genome is a complex blueprint. This instruction booklet—or genetic code—differs in each individual. 

Mutations in DNA trigger normal cells to change, which is how cancer develops and spreads. Researchers seeking to explore the foundations of cancer made great strides throughout the 20th century. The advent and rise of new technologies led to bold leaps into the unknown that spurred exponential growth in research.

In 2003, scientists at the National Institutes of Health’s Human Genome Project announced they had sequenced the entire human genome for the first time. Through this project, we gained insight into the number of genes and the organization of the genome’s base pairs. The undertaking cost roughly $3 billion, involved 20 institutions and took 10 years to complete.

Technology quickly advanced, resulting in rapid sequencing capacity at a reduced cost. Now, scientists could contemplate sequencing the entire genome of an individual. In 2008, this was achieved for the first time in a cancer patient, a middle-aged woman with acute myeloid leukemia.

At the time, large-scale sequencing projects were focused squarely on adult cancers. Leaders at St. Jude Children’s Research Hospital saw an opportunity to fill a void and define the genomic landscape of pediatric cancer, including some of the least understood and most challenging cancers.

What began in 2010 as the largest investment and most comprehensive effort to identify and understand the genetic origins of cancer resulted in a remarkable decade of discovery, stemming from a bold initiative known as the Pediatric Cancer Genome Project.

“The Pediatric Cancer Genome Project has had a profound impact on our understanding of the genetic lesions that drive the formation of pediatric cancer and how resistance to treatment develops,” said St. Jude president and CEO James R. Downing, MD, who is the project’s architect and who was the hospital’s scientific director at the time of its launch. “In turn, this information has had a direct impact on the way we diagnose, risk-stratify and treat pediatric cancer patients.”

The Announcement

The scientific research community turned its focus to Washington, D.C., in January of 2010, when details of the Pediatric Cancer Genome Project were unveiled at a press conference at the National Press Club. 

St. Jude and St. Louis-based Washington University School of Medicine announced the $65 million, three-year endeavor to decode the genomes of 600 childhood cancer patients, who contributed tumor and normal tissue samples for the historic effort.

Both institutions would contribute funding, work and expertise. Scientists would ultimately sequence the entire genomes of normal and cancer cells from 800 patients, comparing differences in the DNA to find genetic mistakes that lead to cancer. 

William Evans, PharmD, Pharmaceutical Sciences, who served as the hospital’s director and CEO from 2004 to 2014, described how the project set the stage for a revolution in our understanding of the origins of cancer.

“For the first time in history, we have the tools to identify all of the genetic missteps that turn a white blood cell into a leukemia cell or a brain cell into a brain tumor,” Evans said during the press conference. “We believe that identifying mutations in DNA that drive the malignant transformation will provide the foundation for advances in 21st century cancer diagnosis and treatment.”

The Time is Right

During the event, Downing referenced how St. Jude was uniquely positioned to take on the project, saying that it was the hospital’s mission “to take on the toughest cases, and the toughest research problems go hand-in-hand with that.

“We have been asking ourselves for more than 10 years, ‘When will it be the right time to do this kind of full DNA sequencing?’ We feel the time is right,” Downing said at the 2010 press conference.

Among the presenters at the event was Francis Collins, MD, PhD, director of the National Institutes of Health. Collins led the Human Genome Project, which paved the way for genetic research projects.

“What is done in this partnership between St. Jude and Washington University will provide the foundation upon which pediatric cancer diagnostics and therapeutics will be built in the future,” Collins said.

Visit stjude.org/pcgp in the coming months to keep up with how the project built a research engine that is moving medicine forward.