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Technique could speed new medulloblastoma drugs

al wiring system and a light bulb," Gilbertson said. "You know if a certain part of the wiring network is working if the light bulb connected to it is on. In the medulloblastoma cell, the wiring is composed of proteins making up the specific signaling pathway that is abnormally activated by a gene mutation, and the light bulb is the group of genes that the pathway causes to be over-expressed." The St. Jude team showed in samples of medulloblastoma from different groups of children that it is possible to determine which gene mutations are present in tumors by studying which genes are expressed by those tumors.

"Since each of these gene expression signatures is regulated by a specific pathway, these genes essentially report to us which pathway might be causing the cancer," Gilbertson said. "Using this information, researchers can use drugs to block that pathway."

The St. Jude team proved that the principle of identifying genes linked to abnormal signaling pathways is valid by generating gene expression profiles from 46 medulloblastoma samples. The investigators identified five medulloblastoma subgroups that differed from each other by their patterns of gene expression. These subgroups also differed according to their histologic (microscopic) characteristics and by how they behaved in patients.

For example, medulloblastomas in subgroup B occurred in patients who were older than 3 years and whose cancer was of the standard or classic type usually recognized under the microscope. In contrast, medulloblastomas in subgroup D occurred in children younger than 3 years, and these tumors had different characteristics from those in subgroup B.

The investigators showed that activation of different signal pathways contributes to the different medulloblastoma gene expression signatures found in each subtype. For example, the team found that genes in a pathway called WNT are especially active in tumors from subgroup B, while genes in the SHH pathway are e
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Contact: Bonnie Kourvelas
media@stjude.org
901-495-3306
St. Jude Children's Research Hospital
17-Apr-2006


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