Washington University School of Medicine in St. Louis and St. Jude Children’s Research Hospital have announced an unprecedented effort to identify the genetic changes that give rise to some of the world’s deadliest childhood cancers. The team has joined forces to decode the genomes of more than 600 childhood cancer patients, who have contributed tumor samples for this historic effort.
The St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project is the largest investment to date — estimated to cost $65 million over three years — aimed at understanding the genetic origins of childhood cancers. Scientists involved in the project will sequence the entire genomes of both normal and cancer cells from each patient, comparing differences in the DNA to identify genetic mistakes that lead to cancer. Kay Jewelers, a long-standing supporter of St. Jude Children’s Research Hospital, has committed to providing $20 million as lead sponsor of this project.
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“We are on the threshold of a revolution in our understanding of the origins of cancer,” says William E. Evans, Pharm.D., St. Jude director and chief executive officer. “For the first time in history, we have the tools to identify all of the genetic abnormalities that turn a white blood cell into a leukemia cell or a brain cell into a brain tumor. We believe it is from this foundation that advances for 21st-century cancer diagnosis and treatment will come.”
Memphis-based St. Jude is home to one of the world’s largest and most complete repositories of biological information about childhood cancer. The collection dates to the 1970s and includes more than 50,000 tumor, bone marrow, blood and other biological samples. These samples are essential to efforts to understand the origins of cancer. The tissue bank has also helped St. Jude scientists develop the experimental models expected to be important for determining which mutations drive cancer’s development and spread.
The collaboration focuses on childhood leukemias, brain tumors and tumors of bone, muscle and other connective tissues called sarcomas. St. Jude will provide DNA from tumor and normal tissues of patients, Washington University’s Genome Center will perform the whole genome sequencing, and both will participate in validation sequencing. Researchers at both institutions will collaborate to analyze the data and make the information publicly available once validated. Prior research by this group and others indicates that the many genetic abnormalities in childhood cancers will differ from those found in adult cancers.
“This extraordinary partnership will add a new dimension to our understanding of childhood cancers,” says pediatric geneticist Larry J. Shapiro, M.D., executive vice chancellor for medical affairs and dean of Washington University School of Medicine. “A genome-wide understanding of cancer offers great promise for developing powerful new approaches to diagnose and treat cancer or perhaps even to prevent it. In the short term, the project will yield key genetic information that may ultimately help physicians choose the best treatment options for young cancer patients.”
Scientists at Washington University’s Genome Center pioneered whole‐genome sequencing of cancer patients genomes. In 2008, Richard Wilson, Ph.D., director of the center, along with co-director Elaine Mardis, Ph.D., and Timothy Ley, M.D., the Alan and Edith Wolff Professor of Medicine, and colleagues became the first to decode the complete genome of a cancer patient and trace the disease to its genetic roots. They have since sequenced the genomes of additional cancer patients, including those with breast, lung and ovarian tumors and glioblastoma, a type of brain tumor. These studies have identified intriguing and unexpected genetic connections between patients with different types of cancer that likely would not have been discovered using conventional approaches.
Earlier research to identify cancer mutations has typically focused only on the few hundred genes already suspected of being involved in the disease. While a few recent studies have involved sequencing the 20,000 or so protein-coding genes in the genome, the whole-genome approach involved in this collaboration provides a more detailed and complete picture of all the mutations involved in a patient’s cancer by examining both the protein-coding genes and the long stretches of DNA between genes, which may influence the ways the genes work. Such complete genomic sequencing is now possible because of recent advances that have made the technology faster and far less expensive.
Researchers involved in the project also will investigate how pediatric cancer is influenced by variations in the genome, including epigenetic changes, which alter the expression of genes but not the genes themselves. They also will use DNA sequencing data to identify genetic markers that can help physicians decide the best treatment options for cancer patients based on the genetic profile of their tumors.
The project’s scope and design reflects the philosophies and talents of the institutions involved. St. Jude and Washington University have a history of scientific collaboration and a track record of innovation in patient care. They also share a commitment to excellence and openness in research. The pediatric genome project will include a public database where information, once validated, will be shared with the international scientific community, with the goal of accelerating progress against childhood cancer.
While great progress has been made in treating childhood cancer, it is still the leading cause of death from disease among U.S. children over one year of age, and cure rates for some childhood cancers remain below 50 percent.
More information about the project can be found at pediatriccancergenomeproject.org
Washington University School of Medicine
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes Jewish Hospital, currently ranked ninth among the nation’s best hospitals by U.S. News & World Report, and St. Louis Children’s Hospital, named among the nation’s elite pediatric hospitals by U.S. News & World Report, the School of Medicine is linked to BJC HealthCare. Washington University and Barnes‐Jewish Hospital are also home to the Siteman Cancer Center, a federally designated Comprehensive Cancer Center. For more information, medicine.wustl.edu.
Washington University’s Genome Center
The Genome Center at the Washington University School of Medicine is a world leader in high‐speed, large‐scale sequencing of genomes, from primitive bacteria to complex humans. The Center played a key role in the Human Genome Project, contributing 25 percent of the finished sequence. The Center currently receives substantial funding from the National Institutes of Health for research that includes the Cancer Genome Atlas Project, to sequence the DNA of adult cancer patients and their tumors to identify the genetic changes important to cancer; the Human Microbiome Project, to sequence the genomes of bacteria involved in human health and disease; and the 1,000 Genomes Project, to catalog the immense human variation written into the genetic code. For more information, genome.wustl.edu.
St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is internationally recognized for its pioneering research and treatment of children with cancer and other catastrophic diseases. Ranked the No. 1 pediatric cancer hospital by Parents magazine, St. Jude is the first and only NCI‐designated Comprehensive Cancer Center devoted solely to children, and has treated children from all 50 states and from around the world. St. Jude has developed research protocols that helped push overall survival rates for childhood cancer from less than 20 percent when the hospital opened to almost 80 percent today. St. Jude is the national coordinating center for the Pediatric Brain Tumor Consortium and the Childhood Cancer Survivor Study. In addition to pediatric cancer research, St. Jude is also a leader in sickle cell disease research and is a globally prominent research center for influenza.
Founded in 1962 by the late entertainer Danny Thomas, St. Jude freely shares its discoveries with scientific and medical communities around the world, publishing more research articles than any other pediatric cancer research center in the United States. St. Jude treats over 5,400 patients each year and is the only pediatric cancer research center where families never pay for treatment not covered by insurance. St. Jude is financially supported by thousands of individual donors, organizations and corporations without which the hospitals’ work would not be possible. For more information, go to www.stjude.org.