A top pediatric cancer hospital is teaming up with a leading genomics center to indentify the genetic changes that give rise to some of the world’s deadliest childhood cancers. St. Jude Children’s Research Hospital and Washington University School of Medicine in St. Louis say the have joined forces to decode the genomes of more than 600 childhood cancer patients who have contributed tumor samples for this $65 million effort over three years.

 

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.

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.

 

“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,” says William Evans, St. Jude director and CEO. “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 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.

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 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.

 

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.

 

“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,” says pediatric geneticist Larry Shapiro, executive vice chancellor and dean of Washington University School of Medicine.  “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.”