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Scientists find potential drug targets in deadly pediatric brain tumors
Date:4/6/2014

orative "precision medicine" clinical trial based at Dana-Farber/Boston Children's. This trial was specifically designed to make discoveries that would change the treatment for children with a type of high grade astrocytoma called diffuse intrinsic pontine glioma (DIPG), the most aggressive brain tumor in children. DIPGs develop in the brainstemthe seat of crucial, basic body functions that keep people aliveand are therefore impossible to remove safely with surgery.

Doctors and patients from more than 20 institutions have now joined this study, which requires taking a biopsy from 100 children, analyzing their tumor tissue using pathology and molecular testing, and planning treatment specifically for each patient based on the results. A goal of the study is to determine whether advanced DNA sequencing and other tools that search for abnormalities and biomarkers can be used to guide potential treatments.

"Instead of treating all the patients the same, this trial obtains a biopsy at the time of diagnosis and the treatment is determined by the expression pattern of the tumor," says Kieran.

Findings in the Nature Genetics study include analysis of biopsy samples from the first group of children enrolled in the trial. In all, 40 tumor specimens underwent sequencing; 25 were from patients with DIPG tumors, some of whom were on the trial.

Most of the tumors were found to harbor a mutation called K27M in the H3F3A protein that is a basic building block of the "epigenome." The effects of this mutation are termed epigenetic because they can change the level of gene activity without changing the structure of a gene's DNA. Mutations in H3F3A have recently been detected in a large percentage of pediatric high-grade astrocytomas, but effective drugs for this mutation have not yet been found.

However, the scientists found that H3F3A mutations always occurred with other mutations that could in theory be targeted by existing d
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Contact: Irene Sege
irene.sege@childrens.harvard.edu
617-919-7379
Dana-Farber Cancer Institute
Source:Eurekalert  

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