Notch Cell Signaling Pathway Linked To Brain Tumors In Children

In one of the latest developments in cell signaling research, the cell communication pathway known as Notch has been linked to a type of brain tumor that occurs in children. In a study recently published in the Journal of Neuropathology & Experimental Neurology, it was announced that Notch genes were ‘overexpressed’ in cases of pilocytic astrocytoma (PA).

 

Although one of most commonly occurring types of tumors in children, PA is a relatively rare disease. Considered a low-grade, slow-growing brain tumor, PA has been diagnosed in 15% of all primary brain tumors cases in adolescents and children. According to statistics gathered by the Central Brain Tumor Registry of the United States, one out of 100,000 children in the United States develops PA every year.

 

PA is commonly treated via surgery, which can be an effective solution. However, many cases of PA involve tumor growth in hard-to-reach areas of the brain. Left untreated, PA eventually results in seizures, loss of vision, and difficulty with physical coordination.

 

The discovery of Notch’s significance with regard to tumor growth was made by a research team headed by Fausto Rodriguez, M.D. of the John Hopkins Kimmel Cancer Center. Rodriguez, who is also an associate professor of pathology at the Johns Hopkins University School of Medicine, said that the discovery of the pathway’s actions was made during a comparison of the amount of RNA produced by the genes–in a process known as ‘expression’–which occurs in brain tissue. The study involved both healthy tissue and samples from patients with PA.

 

The results of the study showed that one or more of the genes found in the Notch pathway were overexpressed in almost all 22 samples obtained from PA brain tissue. In comparison, the healthy brain cells showed normal levels of expression. Of the 22 samples, four to 21 showed signs of overexpression. Proteins closely related to Notch–HES1 in particular–were also detected in 58 out of 61 additional brain tissue samples. Of those samples, 40 displayed expression in varying degrees.

 

Rodriguez further explained the Notch pathway as a basic signaling path that enables cellular communication during the development stage. Doctors already know that cancer triggers the abnormal activation of signaling pathways, effectively spurring on the growth of tumor cells and ensuring its survival. According to Rodriguez, the results of the new study support that discovery, and that the actions of the Notch pathway have been identified in cancers such as leukemia and breast cancer.

 

Co-authored by Charles Eberhart, M.D., also of John Hopkins, the study also revealed the significance of the Notch pathway in cases of medulloblastoma and glioblastoma, two other types of brain cancer that have a significantly higher risk of death than PA. According to Rodriguez, their study conclusively proved that Notch was abnormally active in low-grade tumors such as PA. He also suggests that Notch may one day serve as the primary target in the treatment of PA and other tumors for which surgery is dangerous and/or impossible due to the location of the tumor.