Featured Research

from universities, journals, and other organizations

Mutation discovery may improve treatment for rare brain tumor type

Date:
January 12, 2014
Source:
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Summary:
Scientists have identified a mutated gene that causes a type of tenacious, benign brain tumor that can have devastating lifelong effects. Currently, the tumor can only be treated with challenging repeated surgeries and radiation.

Scientists have identified a mutated gene that causes a type of tenacious, benign brain tumor that can have devastating lifelong effects. Currently, the tumor can only be treated with challenging repeated surgeries and radiation.

Related Articles


The discovery, reported in Nature Genetics, is encouraging, because it may be possible to attack the tumors with targeted drugs already in use for other kinds of tumors, said the investigators from Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard.

The mutated gene, known as BRAF, was found in almost all samples of tumors called papillary craniopharyngiomas. This is one of two types of craniopharyngiomas -- the other being adamantinomatous -- that develop in the base of the brain near the pituitary gland, hypothalamus, and optic nerves. The papillary craniopharyngiomas occur mainly in adults; adamantinomatous tumors generally affect children.

The researchers identified a different mutant gene that drives the tumors in children. Drugs that target these adamantinomatous tumors are not yet clinically available, but may be in the future, said the researchers.

"From a clinical perspective, identifying the BRAF mutation in the papillary tumors is really wonderful, because we have drugs that get into the brain and inhibit this pathway," said Sandro Santagata, MD, PhD, a co-senior author of the paper. "Previously, there were no medical treatments -- only surgery and radiation -- and now we may be able to go from this discovery right to a well-established drug therapy." BRAF inhibitors are currently used in treating malignant melanoma when that mutation is present.

Priscilla Brastianos, MD, co-first author of the study, and Santagata said plans are underway to design a multicenter clinical trial to investigate the efficacy of a BRAF inhibitor in patients with papillary craniopharyngiomas.

Craniopharyngiomas occur in less than one in 100,000 people. They are slow-growing tumors that don't metastasize, but they can cause severe complications, including headaches, visual impairment, hormonal imbalances, obesity and short stature. Even with expert neurosurgery, it is difficult to completely remove the tumors without damaging normal structures, and the tumors often recur.

The investigators were surprised to find that the single mutated BRAF gene was the sole driver of 95 percent of the papillary craniopharyngiomas they analyzed with whole-exome DNA sequencing. "We were really surprised to find that something as simple as a BRAF mutation by itself, rather than multiple mutations, is what drives these tumors," said Santagata.

One scenario, should the inhibitors prove successful in halting or reversing growth of the tumors, would be to test the drugs preoperatively with the aim of shrinking the tumor so less radical surgery would be needed, said Santagata.

A different mutation, in a gene called CTNNB1, was identified as the principal abnormality in the pediatric tumors, according to the report. This mutation causes overactivity in the beta-catenin molecular growth-signaling pathway. Unlike with the BRAF mutation, drugs that inhibit the CTNNB1 abnormality have not yet reached the clinic, but several groups are working on them, Santagata said.


Story Source:

The above story is based on materials provided by Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Priscilla K Brastianos, Amaro Taylor-Weiner, Peter E Manley, Robert T Jones, Dora Dias-Santagata, Aaron R Thorner, Michael S Lawrence, Fausto J Rodriguez, Lindsay A Bernardo, Laura Schubert, Ashwini Sunkavalli, Nick Shillingford, Monica L Calicchio, Hart G W Lidov, Hala Taha, Maria Martinez-Lage, Mariarita Santi, Phillip B Storm, John Y K Lee, James N Palmer, Nithin D Adappa, R Michael Scott, Ian F Dunn, Edward R Laws, Chip Stewart, Keith L Ligon, Mai P Hoang, Paul Van Hummelen, William C Hahn, David N Louis, Adam C Resnick, Mark W Kieran, Gad Getz, Sandro Santagata. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nature Genetics, 2014; DOI: 10.1038/ng.2868

Cite This Page:

Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "Mutation discovery may improve treatment for rare brain tumor type." ScienceDaily. ScienceDaily, 12 January 2014. <www.sciencedaily.com/releases/2014/01/140112190723.htm>.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center. (2014, January 12). Mutation discovery may improve treatment for rare brain tumor type. ScienceDaily. Retrieved March 28, 2015 from www.sciencedaily.com/releases/2014/01/140112190723.htm
Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "Mutation discovery may improve treatment for rare brain tumor type." ScienceDaily. www.sciencedaily.com/releases/2014/01/140112190723.htm (accessed March 28, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, March 28, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com
WH Plan to Fight Antibiotic-Resistant Germs

WH Plan to Fight Antibiotic-Resistant Germs

AP (Mar. 27, 2015) — The White House on Friday announced a five-year plan to fight the threat posed by antibiotic-resistant bacteria amid fears that once-treatable germs could become deadly. (March 27) Video provided by AP
Powered by NewsLook.com
House Ready to Pass Medicare Doc Bill

House Ready to Pass Medicare Doc Bill

AP (Mar. 26, 2015) — In rare bipartisan harmony, congressional leaders pushed a $214 billion bill permanently blocking physician Medicare cuts toward House passage Thursday, moving lawmakers closer to resolving a problem that has plagued them for years. (March 26) 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