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Key mutations discovered for most common childhood brain cancer
Date:7/22/2012

the biological basis of the tumor's variability. "For the first time, we'll be able to classify and treat medulloblastoma based on molecular typing, providing the best therapy with the fewest long-term consequences."

In this new study, Pomeroy and his team used next generation sequencing technologies to read the full complement of protein-coding genes (also called the exome) of tumors from 92 patients. Within these tumors the team discovered that somatic (that is, non-heritable) mutations occur at very low frequency, one-tenth to one-hundredth of that seen in cancers of adults. Specific gene mutations clustered neatly into the four molecular subtypes, although the majority of genes (88%) were mutated only once in the entire tumor collection. Only 12 genes were mutated in more than one tumor, illustrating medulloblastoma's genetic heterogeneity.

Functionally, the mutated genes fell into two broad categories: genes like Shh and Wnt that play direct roles in molecular pathways controlling cell growth, and genes like DDX3X and GPS2 that play more of a coaching role, modulating the activity of other genes.

Taken as a whole, the study's results confirm the view of medulloblastoma as a family of tumors driven by disruptions in just a few common mechanisms. However, the form those disruptions takethe actual mutations or genomic changescan vary from tumor to tumor.

"The results reflect two emerging genetic themes seen throughout childhood tumors," Pomeroy noted. "First, very low mutation rates, much lower than those seen in adult tumors, and second, the importance of mutations in genes that regulate the function of the cell's growth pathways but which aren't direct components of those pathways."

Some of the study's findings could be translated to patients relatively quickly. For instance, with the main mutations of each subtype in hand, it should soon be possible to rapidly classify individual medulloblastoma patients' tumors an
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Contact: Meghan Weber
meghan.weber@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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