St. Jude Children's Research Hospital and the McDonnell Genome Institute at Washington University School of Medicine in St. Louis have joined forces to decode the genomes of more than 600 childhood cancer patients. 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.
St. Jude Children’s Research Hospital and Washington University School of Medicine in St. Louis, announced on January 25, 2010 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.
“We are on the threshold of 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 abnormalities that turn a white blood cell into a leukemia cell or a brain cell into a brain tumor,” said Dr. William E. Evans, St. Jude director and chief executive officer. “We believe it is from this foundation that advances for 21st century cancer diagnosis and treatment will come.”
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 McDonnell Genome Institute 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 Dr. Larry J. Shapiro, executive vice chancellor 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 McDonnell Genome Institute pioneered whole-genome sequencing of cancer patients’ genomes. In 2008, they became the first to decode the complete genome of a cancer patient – a woman with leukemia – and trace her 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.
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.
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.
One of only three NIH-funded large-scale genome centers in the United States, the McDonnell Genome Institute at Washington University is a leader in genomics research as it applies to the study of biology, human disease and the field of personalized medicine. Founded in 1993, The McDonnell Genome Institute focuses on cancer genomics, the genomics of heritable diseases, microbial and pathogen genomics, as well as novel sequencing and evolutionary genomics. For more information, genome.wustl.edu.
Acute Myeloid Leukemia M7: This is a rare subtype of pediatric Acute Myeloid Leukemia.
Adrenocortical Tumor: This cancer affects the adrenal cortex, a steroid hormone-producing tissue. It often affects children under 6.
B-cell Precursor Acute Lymphoblastic Leukemia: This is the most common type of Acute Lymphoblastic Leukemia.
Choroid Plexus Carcinoma: This form of cancer affects the choroid plexus region of the brain, an area that produces cerbrospinal fluid. It generally affects very young children.
Core Binding Factor Acute Myeloid Leukemia: This is a form of leukemia that if detected, can result in complete remission.
E2A-PBX Acute Lymphoblastic Leukemia (ALL): This is a form of ALL associated with a fusion of the genes E2A and PBX.
Ependymoma: This cancer affects the ependyma, a central nervous system tissue. In children these tumors are often found intracranially.
ETS Related Gene-associated Acute Lymphoblastic Leukemia (ALL): This is a form of ALL associated with the ETS-Related Gene.
ETV-associated Acute Lymphoblastic Leukemia (ALL): This is a form of ALL associated with a fusion between ETV-6 and AML-1.
Ewings Sarcoma: This is a rare disease where cancer cells are found in the bone or soft tissue.
High Grade Glioma: This type of cancer arises from the glial cells in the brain and tends to have a poor prognosis.
Hyperdiploid Acute Lymphoblastic Leukemia: This form of leukemia characterized by a gain of chromosomes. It is a common malignancy in children.
Hypodiploid Acute Lymphoblastic Leukemia: This is a rare form of leukemia characterized by an absence of chromosomes. It primarily affects young adults.
Infant Acute Lymphoblastic Leukemia: This is the most common type of leukemia in children under age 15.
Low Grade Glioma: This is a slow-growing brain tumor that affects children. It is a very common type of brain tumor in children.
Medulloblastoma: This is a severe form of brain tumor that is common among children under age 20.
Melanoma: Melanoma, or skin cancer, is relatively rare in the pediatric population but has similar survival rates as the adult version.
Neuroblastoma: This cancer develops from nerve tissue and occurs in infants and children.
Osteosarcoma: This cancer affects the bone often during rapid growth that occurs during adolescence.
Ph+ Acute Lymphoblastic Leukemia: This is a form of leukemia associated with the Philadelphia chromosome translocation.
Retinoblastoma: This cancer affects the eye's retina and develops mostly in children under the age of 6.
Rhabdomyosarcoma: This soft tissue cancer is most often found in children.
T-cell/Acute Lymphoblastic Leukemia: This form of blood cancer affects white blood cells called T cells.