Key St. Jude Genomic Discoveries
Cancer is triggered by harmful mutations in the genes of normal cells. If scientists can pinpoint the underlying genetic mutations that cause a normal cell to become cancer, it has the potential to lead to new medicines and to optimize the use of current therapy. Although researchers worldwide have extensively studied cancer genetics, the vast numbers of genetic changes that lead to cancer have not been identified, and as a result, the true genetic causes of most cancers remain elusive.
For the last two decades, St. Jude Children’s Research Hospital has been the leader in identifying the underlying genetic abnormalities of childhood cancers. St. Jude researchers have made key discoveries about leukemia, brain tumors and the eye cancer retinoblastoma, as well as how children’s DNA influence their response to certain medications. With each piece of information uncovered, researchers devise new ways to fight cancer with more effective, less toxic treatments.
Here are recent examples of how St. Jude genetic research is impacting childhood cancer:
- St. Jude researchers have championed efforts to understand the genetic mistakes that give rise to pediatric acute lymphoblastic leukemia (ALL) and identifying a new chromosomal abnormality responsible for some cases. The research focused on the link between a deletion in a chromosome and a form of ALL that is particularly common in children with Down syndrome. The discovery has already resulted in new diagnostic tests and potential tools for tracking these patients’ response to treatment.
- St. Jude researchers published the first complete search of the human genome for inherited risk factors of pediatric acute lymphoblastic leukemia, researchers identified variations in two genes that account for 37 percent of cases of this cancer, including a gene that may help predict drug response. Importantly, the research was the first proof based on a complete survey of the human genome, that inheritance plays a role in childhood ALL.
- St. Jude researchers launched the most comprehensive analysis yet of the genome for childhood acute myeloid leukemia (AML) and found only a few abnormalities in the genetic blueprint, suggesting this cancer arises from just a handful of missteps. Researchers were surprised to find that the development of pediatric AML may require fewer genetic alterations than other cancers.
- St Jude researchers built upon previous genetic studies to pinpoint a new class of gene mutations that identify cases of ALL that have a high risk of relapse and death. Their finding suggested specific drugs that could treat this high-risk leukemia subtype in children, using drugs that are already in clinical trials for similar blood diseases in adults.
- St. Jude researchers identified a gene abnormality that predicts which patients with ALL are more likely to relapse. For doctors, this could lead to a genetic test to identify children at high risk of relapse—and if the abnormality were identified, physicians could assign more aggressive treatment in hopes of warding off relapse.
- St. Jude researchers discovered that individual children with ALL respond differently to the same drug treatment, and that the variance could be explained by differences in the child’s genetics. The insights gained in the study work toward the effort to individualize chemotherapy according to a patient’s genetics.
- In a series of experiments of unprecedented breadth, St. Jude researchers gained a better look at the mutational landscape of ALL, discovering previously unsuspected mutations that contribute to the formation of the disease. The study was a watershed moment in pediatric cancer research, demonstrating that it is possible to significantly speed the identification of the genetic lesions that are the underlying cause of not only ALL but also many other cancers, including those affecting adults.
- St. Jude researchers studying the eye cancer retinoblastoma determined how the disease is triggered by genetic loss of a protective mechanism that normally kills aberrant cells. Based on these findings, researchers demonstrated in the laboratory, a new, locally applied treatment for retinoblastoma that not only greatly reduced the size of the tumor, but did so without causing the side effects common with standard chemotherapy.
- St. Jude researchers determined that the patterns of gene expression in tumor samples show us how brain tumors called ependymomas arise from rare stem cells in the nervous system and how targeted treatment of specific signal pathways can advance care of solid tumor patients.
- St. Jude researchers identified a specific pattern of gene expression linked to multiple-drug resistance of leukemic cells, providing crucial information into why standard therapies fail to cure some children with ALL.