Results from a recent clinical study show that distinct subtypes of glioblastoma tend to develop in different regions of the brain. These results elucidate how the same cancer-causing mutation can result in different types of brain malignancies. Glioblastoma is the most common type of brain cancer in adults.1
“It is now well-documented that cancers that look the same under the microscope actually contain different genetic changes, or mutations, and respond differently to therapy,” said Clark Chen, MD, PhD, vice-chair of research and academic development in the Division of Neurosurgery at University of California San Diego School of Medicine, and senior author of the study.
“What remains unclear is how the exact same mutation can give rise to different subtypes of tumor.”
Researchers created a new computational method to define where different subtypes of glioblastoma develop in the brain. Using clinical images from 217 patients with brain tumors, the researchers discovered that the proneural and neural glioblastoma subtypes usually occurred closer to the center of the brain, in the subventricular zone (SVZ). The mesenchymal and classical glioblastoma subtypes, however, developed farther from the SVZ.
The SVZ contains neural stem cells, which can give rise to all cell types in the brain. During development, neural stem cells migrate out from the SVZ and differentiate into the different cell types that comprise the human brain.
“Our study suggests that if a cancer-causing mutation occurs in the neural stem cell population in the SVZ, it gives rise to the proneural or the neural glioblastoma subtype. On the other hand, if the same mutation occurs in a different cell population located farther away from the SVZ, it will give rise to other subtypes,” Chen explained.
Researchers then used a mouse model of glioblastoma to confirm the importance of location in the brain for determining the subtype of glioblastoma. In the mouse model, all glioblastomas arise from the same mutations, yet the tumors that formed closer to the SVZ were more likely to be neural and proneural subtypes. Similarly, the tumors that formed farther away were more likely to be classical or mesenchymal subtypes.
1. Steed TC, Treiber JM, Patel K, et al. Differential localization of glioblastoma subtype: implications on glioblastoma pathogenesis [published online ahead of print April 1, 2016]. Oncotarget. doi:10.18632/oncotarget.8551.