Neuropathology Division
   Brain Tumor Research

Our Pilocytic/Pilomyxoid Astrocytoma Research

MRI image of a brain

Our group is focused on:

  1. defining the microscopic appearance and clinical spectrum of piloid tumors, in particular the relationship between pilocytic and pilomyxoid astrocytomas
  2. identifying the genetic changes that cause pilocytic/pilomyxoid tumors and other pediatric low grade gliomas to grow
  3. eveloping new models of pilocytic/pilomyxoid tumors and other pediatric low grade gliomas
  4. testing novel therapies that target pilocytic/pilomyxoid tumors and other pediatric low grade gliomas

Some of our findings are discussed below.

Discovery of the Pilomyxoid Astrocytoma

Dr. Burger published the first description of pilomyxoid astrocytomas in 1999, and has subsequently been involved in six additional studies of these tumors. Dr. Burger’s current research goal is to more precisely define the relationship between pilomyxoid and pilocytic astrocytomas. In some patients, tumors can have a mixed appearance, or change from a pilomyxoid lesion to a pilocytic one over time, suggesting that the two are not entirely distinct entities.

Identification of a Common Molecular Change in Pilocytic Astrocytomas – Potential For New Treatments

Figure one
Figure 1 - By labeling tumor DNA and binding it to probes from over 200,000 areas of the human chromosome, we were able to identify a region of DNA which was duplicated in the tumor. This is outlined by the blue box and red line, and contains the BRAF gene at one end.

We have recently completed an initial molecular analysis of genomic changes in 25 pilocytic astrocytomas, and published our findings in the Journal of Neuropathology and Experimental Neurology. We found a number of genetic changes in these tumors, and are particularly excited by our discovery that a gene called “BRAF” was altered in the majority of cases (Figure 1). Several drugs have been developed that inhibit the pathway activated by BRAF, and we hope to test the ability of these to slow or stop the growth of pilocytic astrocytomas and other pediatric gliomas.

New Models of Pediatric Gliomas

Microscopic closeup
Figure 2 - We have been able to grow pilocytic astrocytoma cells as floating "spheres" in culture media used to sustain brain stem cells.

Unfortunately, no good models of sporadic pilocytic or pilomyxoid astrocytomas currently exist, making it difficult to evaluate new therapies. We are therefore developing new pediatric glioma models that will make it possible to test the effects of drugs targeting BRAF and other molecular pathways. We are currently pursuing several experimental approaches. First, we are growing pilocytic astrocytomas and other pediatric gliomas resected at Johns Hopkins in culture using several techniques. Shown in Figure 2 is a pilocytic astrocytoma “neurosphere” growing in our laboratory. We are also attempting to grow these cells by injecting them into mouse brains. Finally, we are adding activated BRAF and other oncogenes to various human stem and precursor cells in an attempt to generate gliomas resembling those that arise in children.