Featured Research

from universities, journals, and other organizations

Clues to cause of kids' brain tumors

Date:
November 16, 2012
Source:
Washington University School of Medicine
Summary:
Insights from a genetic condition that causes brain cancer are helping scientists better understand the most common type of brain tumor in children.

Mouse brain. An abnormal version of the BRAF protein (shown in red) from a mouse brain with a low-grade brain tumor. Scientists have shown that in certain cells, this protein can cause the cells to proliferate rapidly, leading to tumor formation.
Credit: David Gutmann, MD, PhD

Insights from a genetic condition that causes brain cancer are helping scientists better understand the most common type of brain tumor in children.

Related Articles


In new research, scientists at Washington University School of Medicine in St. Louis have identified a cell growth pathway that is unusually active in pediatric brain tumors known as gliomas. They previously identified the same growth pathway as a critical contributor to brain tumor formation and growth in neurofibromatosis-1 (NF1), an inherited cancer predisposition syndrome.

"This suggests that the tools we've been developing to diagnose and treat NF1 may also be helpful for sporadic brain tumors," says senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology.

The findings appear Dec. 1 in Genes and Development.

NF1 is among the most common tumor predisposition syndromes, but it accounts for only about 15 percent of pediatric low-grade gliomas known as pilocytic astrocytomas. The majority of these brain tumors occur sporadically in people without NF1.

Earlier research showed that most sporadic pilocytic astrocytomas possess an abnormal form of a signaling protein known as BRAF. In tumor cells, a piece of another protein is erroneously fused to the business end of BRAF.

Scientists suspected that the odd protein fusion spurred cells to grow and divide more often, leading to tumors. However, when they gave mice the same aberrant form of BRAF, they observed a variety of results. Sometimes gliomas formed, but in other cases, there was no discernible effect or a brief period of increased growth and cell division. In other studies, the cells grew old and died prematurely.

Gutmann, director of the Washington University Neurofibromatosis Center, previously showed that mouse NF1-associated gliomas arise from certain brain cells.

According to Gutmann, the impact of abnormal NF1 gene function on particular cell types helps explain why gliomas are most often found in the optic nerves and brainstem of children with NF1 -- these areas are where the susceptible cell types reside.

With that in mind, Gutmann and his colleagues tested the effects of the unusual fusion BRAF protein in neural stem cells from the cerebellum, where sporadic pilocytic astrocytomas often form, and in cells from the cortex, where the tumors almost never develop.

"Abnormal BRAF only results in increased growth when it is placed in neural stem cells from the cerebellum, but not the cortex," Gutmann says. "We also found that putting fusion BRAF into mature glial cells from the cerebellum had no effect."

When fusion BRAF causes increased cell proliferation, postdoctoral fellows Aparna Kaul, PhD and Yi-Hsien Chen, PhD, showed that it activates the same cellular growth pathway, called mammalian target of rapamycin (mTOR), that is normally also controlled by the NF1 protein. An extensive body of research into the mTOR pathway already exists, including potential treatments to suppress its function in other forms of cancer.

"We may be able to leverage these insights and our previous work in NF1 to improve the treatment of these common pediatric brain tumors, and that's very exciting," Gutmann says.

Gutmann and his colleagues are now working to identify more of the factors that make particular brain cells vulnerable to the tumor-promoting effects of the NF1 gene mutation and fusion BRAF. They are also developing animal models of sporadic pilocytic astrocytoma for drug discovery and testing.


Story Source:

The above story is based on materials provided by Washington University School of Medicine. The original article was written by Michael C. Purdy. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kaul A, Chen Y-H, Emnett RJ, Dahiya S, Gutmann DH. Pediatric glioma-associated KIAA1549:BRAF expression regulates neuroglial cell growth in a cell type-specific and mTOR-dependent manner.. Genes & Development, Dec. 1, 2012

Cite This Page:

Washington University School of Medicine. "Clues to cause of kids' brain tumors." ScienceDaily. ScienceDaily, 16 November 2012. <www.sciencedaily.com/releases/2012/11/121116091226.htm>.
Washington University School of Medicine. (2012, November 16). Clues to cause of kids' brain tumors. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2012/11/121116091226.htm
Washington University School of Medicine. "Clues to cause of kids' brain tumors." ScienceDaily. www.sciencedaily.com/releases/2012/11/121116091226.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins