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Most common brain cancer may originate in neural stem cells
Date:6/1/2009

hways works with other mutations to transform brain cells into cancerous ones.

In the last six years, studies have shown that stem cell-like cells are involved in a number of cancers, including glioblastoma. But the new study specifically reveals that glioblastoma begins in neural stem cells that have a p53 mutation. These cells then give rise to mutated, fast-multiplying cells down the line of cell differentiation a class called transit-amplifying progenitor cells.

"We found that the cells with p53 mutations are highly plastic. If a treatment blocks one path of action, they may learn other ways to grow," Zhu says. That helps explain why glioblastoma multiforme returns in drug-resistant forms.

Research details:

Zhu's team conducted a series of experiments using mice engineered to have a p53 mutation in the central nervous system. They found that a majority developed malignant brain tumors, and that a mutant form of p53 was present in the tumor cells, a phenomenon that is commonly found in human glioblastoma.

"Then we asked, does mutant p53 have any role in tumor initiation and progression? If so, we can use this as a marker for brain cancer in brain cells," says Yuan Wang, the study's first author and a U-M Ph.D. student in cell and developmental biology. The team found that mutant p53 was detectable in a minority of highly proliferative neural stem cells of p53-deficient mice two months after birth, and that the expansion of the mutant-p53-expressing cell population with features of transit-amplifying cells underlies the tumor initiation. The evidence supports the idea that mutant p53 can be a useful marker to trace the glioma cells at all stages.

What's next:

Before any treatments based on these discoveries can benefit people, scientists will need to do more animal studies and verify the animal findings in human studies.

Zhu and his team plan to continue experiments in mice to
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Contact: Nicole Fawcett
nfawcett@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert

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