Johns Hopkins researchers have found a likely explanation for the slow growth of the most common childhood brain tumor, pilocytic astrocytoma. Using tests on a new cell-based model of the tumor, they concluded that the initial process of tumor formation switches on a growth-braking tumor-suppressor gene, in a process similar to that seen in skin moles.
The findings, published in the June 1 issue of Clinical Cancer Research, could lead to better ways of evaluating and treating pilocytic astrocytomas.
"These tumors are slow-growing to start with, and sometimes stop growing, and now we have a pretty good idea of why that happens," says Charles G. Eberhart, M.D., Ph.D., associate professor of Pathology, Ophthalmology and Oncology at Johns Hopkins. "These tumors also can suddenly become more aggressive, which we now think represents an inactivation of this tumor-suppressor gene, and this inactivity could be used as a marker to determine which patients need more therapy."
Pilocytic astrocytoma arises in brain cells known as astrocytes, which, among many functions in the brain, help support neurons. These cancerous astrocytes have DNA mutations that force a growth-related gene, BRAF, into an abnormal, always-on state. Biologists call such cancer-driving genes oncogenes.
Eberhart and his team used a viral gene-transfer technique to deliver an oncogenic, always-on version of BRAF, to fetal brain cells in a lab dish. The idea was to create a cell model of pilocytic astrocytoma, to enable easier study of its growth patterns. As the researchers expected, the cells quickly formed tumorlike colonies but the growth of these colonies soon sputtered out.
The same phenomenon, sparked by an oncogene, was first described six years ago in a study of the biology of skin moles. Moles typically begin in skin cells whose inherited or spontaneous mutations often affecting BRAF drive the cells' growth beyond normal limits. "
|Contact: Vanessa Wasta|
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