Researchers from Children’s Hospital Los Angeles Find Link Between Gene and Brain Tumor Growth
In a ground-breaking study, Anat Erdreich-Epstein, MD, PhD, and colleagues from The Saban Research Institute of Children’s Hospital Los Angeles, are the first to link the level of messenger RNA of the gene PID1 to clinical outcomes of patients with two important types of brain cancer: medulloblastomas and gliomas. Epstein also found that, in vitro, PID1 inhibits cell growth of these two brain cancers as well as a third one, atypical teratoid/rhabdoid tumors (AT/RTs). This study, done in collaboration with a group from Heidelberg, Germany, was published online in the December 3 issue of Clinical Cancer Research.
“In spite of advances, brain cancer continues to be the number 1 cause of illness-related death in children and adolescents,” says Jonathan Finlay, MD, director of the Neuro-Oncology Program at Children’s Hospital Los Angeles. “Dr. Epstein’s findings have the potential to revolutionize therapy and offer more efficient, targeted treatments to patients with malignant brain tumors.”
After analyzing reports of hundreds of medulloblastoma patients, initially in children and later in both children and adults, Epstein found that the level of PID1 coding material, PID1 mRNA, in tumors was highly correlated with the outcome of the patients. Higher levels of PID1 mRNA directly correlated with increased patient survival time. In the test tube, increasing PID1 promoted tumor cell death and reduced the proliferation of the brain cancer cells. Similar correlation of higher PID1 mRNA and longer survival were observed in cohorts of adult patients with glioma. Furthermore, experiments in laboratory cultures of medulloblastoma, AT/RT and glioma cells showed that PID1 has a tumor-inhibitory effect in these brain cancer cells.
“We found a unique correlation between increased expression of the PID1 gene and decreased cancerous brain tumor growth,” says Epstein, who is also an associate professor of Pediatrics and Pathology at the Keck School of Medicine at the University of Southern California. “We will look further into the molecular mechanism of PID1 and use these discoveries to design improved therapies for brain cancer.”
Medulloblastomas and AT/RTs are types of embryonal brain tumors, which arise from immature cells in the brain. They are most common in children under 10 years of age, with medulloblastomas alone accounting for nearly 20% of all pediatric brain tumors. In contrast, gliomas generally occur in older individuals, are the most common malignant brain cancer in adults, and originate from the glial cells of the central nervous system. These cells support and protect the functioning neurons in the brain and spinal cord. Symptoms from these tumors depend on where in the brain they originate.
While the five-year survival rate of children with average-risk medulloblastoma can be between 70 and 80%, the prognosis for patients with high-risk medulloblastoma is not as favorable, and for patients with AT/RT and malignant glioma it remains very poor. Epstein’s laboratory seeks to further understand the molecular functions of PID1 in hopes of designing treatments that increase survival rates and the quality of life for brain tumor patients.
Children's Hospital Los Angeles has been named the best children’s hospital on the West Coast and among the top five in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children’s Hospital is also one of America's premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California.