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Brain tumors and mouse models: New insight into the development of gliomas

In the latest issue of Genes & Development, a team led by Dr. Eric Holland at the Memorial Sloan-Kettering Cancer Centre in New York reports on the development of new mouse models of brain tumors.

Gliomas are the most common form of primary brain tumors, with approximately 30,000 people in the USA newly diagnosed each year. Murine models offer a route to understand how different types and severities of gliomas arise, and an experimental system in which to test potential therapies.

Gliomas are brain tumors that have the characteristics of glial cells. Glial cells are specialised cells whose normal job is to maintain the function and interactions of neurons. Gliomas can show characteristics of either or both types of glial cells, astrocytes and oligodendrocytes. Gliomas are graded according to their severity: Grade 1 are the least serious, while Grade 4 malignant gliomas are the most serious these patients have an average survival time of 1 year from the date of diagnosis.

Previous research has shown that genetic mutations in two different cell signaling pathways can contribute to the formation of gliomas. The first group of mutations disrupt the differentiation process by which an undifferentiated progenitor cell develops into a specific type of glial cell. Such cell signaling pathways are affected by molecules called growth factors, such as platelet derived growth factor (PDGF). The second set of mutations disrupts the cell cycle arrest pathway, which regulates glial cell proliferation.

Based on these findings, Dr. Holland and colleagues used genetic tools to express PDGF in different brain cells to investigate what underlies the different characteristics of gliomas. Two mouse models were generated. One strain of mice expressed excess growth factor in undifferentiated cells, while the second second strain of mice expressed PDGF in differentiated astrocytes. Both strains of mice developed mostly low grade gliomas.

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Contact: Nora Poppito
poppito@cshl.org
Cold Spring Harbor Laboratory
31-Jul-2001


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