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Genomic Alterations in Medulloblastoma

Institution: 
Children's Hospital Los Angeles
Researcher(s): 
Shahab Asgharzadeh, MD
Grant Type: 
Young Investigator Grants
Year Awarded: 
2008
Type of Childhood Cancer: 
Brain Tumors, Medulloblastoma
Project Description: 

Background
Medulloblastoma is a type of brain tumor seen most often in children. Standard treatment for medulloblastoma includes radiation to the whole brain and spine, as well as surgery and chemotherapy. Unfortunately, radiation to the brain has significant long-term side effects in children. These side effects range from mild learning disabilities to severe mental retardation. The brain-damaging effects are most severe in young children.

Recent studies have shown that some (but not all) children can be cured of medulloblastoma using only surgery and chemotherapy. The children in these studies who survived went on to have normal mental function. If we were able to identify ahead of time patients whose medulloblastoma was curable with chemotherapy alone, we could spare many children the devastating effects of radiation. At this time, however, there is no such tool. There is no way to determine which children need radiation therapy, and which children do not.

Project Goal
In our lab, we have looked at "gene expression profiles" from sixteen medulloblastomas. Eleven were from patients who were cured with chemotherapy alone, and five from patients whose tumor grew or came back despite treatment. "Gene expression profiling" is a method of looking at thousands of genes together to find patterns in which genes are "turned on" or "turned off." In this preliminary study, we found, in fact, that the gene expression pattern was significantly different in the tumors that had been cured with chemotherapy than in the tumors that had not. In particular, we found that one gene – a gene called forkhead box G1 (FoxG1) – was a very powerful predictor of how the tumor would behave. In this preliminary study, the gene was turned off in tumors that were curable with chemotherapy, and turned on in tumors that were not.

In the current study involving a larger group of patients, we are trying to find out whether we can accurately identify a gene expression profile that predicts the outcome of children who survived without radiation therapy. Our hope is that in future clinical trials, by measuring the activity of these gene, we will be able to identify the children who may safely avoid radiation. We thus hope to spare many children the long-term devastating side effects of radiation to the brain.