St. Jude, Washington University Launch Genome Project for Childhood Cancers
Researchers at St. Jude Children’s Research Hospital and the Washington University School of Medicine in St. Louis have launched the Pediatric Cancer Genome Project to sequence the genomes of at least 600 children with cancer over the next 3 years. The collaboration marks the first time that whole-genome sequencing will be used on a large scale to discover genetic changes driving pediatric cancers.
“This is the largest and most powerful single initiative in the 50-year history of St. Jude,” the research hospital’s director, Dr. William E. Evans, said at a press briefing announcing the project yesterday. “DNA is being sequenced as we speak,” he added.
St. Jude has a repository of biological samples and clinical information from children who have been treated there since the 1970s. The collection represents a treasure trove of information about cancer, and it can now be scrutinized using the latest genomic technologies at a cost that continues to decline substantially over time.
“This is a new era for pediatric cancers,” NIH Director Dr. Francis Collins said at the briefing. “The study represents an opportunity to discover all the ways that a good cell in an innocent child goes wrong.”
The project—estimated to cost $65 million and funded by St. Jude—aims to discover the genetic origins of pediatric cancers while creating knowledge that can be used to improve the care of young people with these rare diseases. Early results could reveal new uses for available drugs, and, over the long term, lead to targeted agents for these cancers, the researchers said.
New genetic signatures for classifying and treating patients are also anticipated. Knowing that a child has a subtype with a poor prognosis would allow physicians to select aggressive treatments early in the course of the disease. Similarly, doctors could safely withhold treatments from a patient who has a better prognosis, based on a genetic profile.
“These two great NCI-designated comprehensive cancer centers are demonstrating yet again their commitment to making a difference for kids with cancer,” said NCI Director Dr. John Niederhuber.
Dr. Larry J. Shapiro, dean of the Washington University School of Medicine and a pediatric geneticist, said at the briefing: “This project will provide a detailed and complete picture of the mutations in the cancer cells.”
In 2008, researchers at Washington University and their colleagues published the first genome sequence of a person with cancer—a woman with leukemia. They have since published the genome of a second person with leukemia, and they have also sequenced dozens of additional cancer genomes using the same whole-genome approach.
The new effort will focus on leukemias, brain tumors, and sarcomas (tumors of bone, muscle, and other connective tissues). To identify genetic changes associated with cancer, the researchers will sequence DNA from both the tumor cells and normal cells of each patient.
The project complements in every way the efforts of The Cancer Genome Atlas (TCGA) Research Network, which focuses on adult cancers, noted Dr. Collins. Just last week, TCGA investigators identified new subtypes of brain cancer using genomic and clinical data—an example of the kind of knowledge Dr. Collins expects to come from the pediatric project.
Another genome effort in pediatric cancer is the NCI-supported childhood cancer TARGET initiative, which includes St. Jude investigators as well as other childhood cancer researchers. The initial discoveries from this project are being translated to the clinic through an early stage clinical trial that is in development for a newly described type of acute lymphoblastic leukemia.
What distinguishes the new project from past efforts, said Dr. Richard Wilson, director of the Genome Center at Washington University, is that this one will be “all whole-genomes all the time.” Most genome studies have been limited to sets of genes or genetic markers because of the costs of sequencing DNA. Those costs have now fallen to below $100,000 for a tumor-normal combination, and the sequencing can be done in about a week, Dr. Wilson said. (See “A Conversation with Dr. Elaine Mardis” in this issue.)
“There is a sense of urgency to make progress here, and it has now become affordable,” said Dr. Evans. “We see this effort as a marathon, and the first 3 years are really just the beginning. I am certain there will be lots of unanswered questions at the end of this period, and there will be much more work to be done.”
He acknowledged the enormous challenge of managing and making sense of as much as 100 trillion pieces of data (600 cases, 2 genomes per case, and each genome will be sequenced 30 times to ensure that nothing is missed). To meet this challenge, Washington University is adding new instruments and computational power, and the researchers are confident that they are ready.
“The data storage, management, and analysis problems are substantial,” Dr. Wilson said in an interview. “But this project is coming along at just the right time in terms of our technical capabilities. We’ve really come a long way in just the last 6 months in terms of our data production technology.”
St. Jude has, in effect, been preparing for this project for 45 years by creating the tissue repository and developing a capacity for preclinical research studies. The infrastructure and resources required for follow-up studies of the genomic data, such as mouse models, already exist at St. Jude, noted Dr. Elaine Mardis, co-director of the Genome Center at Washington University. “The genome project will fill these pipelines with new information to be analyzed.”
In the future, the project will include other types of alterations in cancer, such as those involving RNA and epigenetic changes, which alter the activity of genes without causing a change in DNA sequence, the researchers said.
They stressed that the results will be made publicly available through a Web site once the information has been validated. The hope is that other investigators will bring their own expertise and perspectives to the data and help move the science forward.
“We view this as creating a resource not just for our efforts but for the world,” said Dr. Evans. He quoted the founder of St. Jude, the entertainer Danny Thomas, who liked to say, “To cure one child in Memphis is to cure a thousand worldwide.”
“It is always a good thing if our discoveries can be amplified and leveraged elsewhere,” Dr. Evans added, “and that’s what has to happen.”
—Edward R. Winstead