Featured Research

from universities, journals, and other organizations

Genomic sequencing identifies mutant 'drivers' of common brain tumor

Date:
January 22, 2013
Source:
Dana-Farber Cancer Institute
Summary:
Large-scale genomic sequencing has revealed two DNA mutations that appear to drive about 15 percent of meningiomas report scientists. Experimental drugs that inhibit these mutant gene pathways are in clinical trials and have shown promising activity.

Large-scale genomic sequencing has revealed two DNA mutations that appear to drive about 15 percent of brain tumors known as meningiomas, a finding that could lead to the first effective drug treatments for the tumors, report scientists from Dana-Farber Cancer Institute and the Broad Institute.

Surgery and radiation currently are the only treatments for meningiomas -- slow-growing, often benign tumors that develop in the membranes surrounding the brain. Meningiomas can grow dangerously large, however, causing seizures and limb weakness, and occasionally are fatal. In some instances, the tumors grow aggressively or their locations make surgery and radiation a challenge to carry out, and chemotherapy has proven ineffective as an alternative.

The researchers report in the journal Nature Genetics that they have identified two mutations, SMO and AKT1, in the genomes of 15 percent of a group of meningiomas removed during surgery. The findings are being published on the journal's web site in advance of appearing in a print edition.

"The wonderful thing about those mutations is that there are already drugs in the clinic to target cancers with those mutations," said Rameen Beroukhim, MD, PhD, a medical oncologist and cancer biologist at Dana-Farber and the Broad Institute.

"Clinically, there is no medical treatment for meningioma that is known to be effective," said Beroukhim, senior author of the paper along with William C. Hahn, MD, PhD, director of the Center for Cancer Genome Discovery at Dana-Farber, and Ian F. Dunn, MD, a neurosurgeon at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC).

Beroukhim said that surgery can effectively treat many meningiomas, but the locations of some tumors make surgery a difficult or impossible option. For other patients, there are not curative treatments, so the discovery of the mutations in some meningiomas "is potentially the first path to an effective medical treatment," Beroukhim noted.

Meningiomas are diagnosed in about 18,000 patients annually in the United States. They account for about one-third of primary brain tumors (those that originate in the brain) and are twice as common in women. They are generally slow-growing, and many patients don't require treatment unless the tumor expands and presses on vital structures. But a significant number recur following treatment, and many become malignant.

Beroukhim said that little has been uncovered about the genetic makeup of meningiomas. In the current study, the scientists sequenced either the entire genome or just the protein-coding regions (exomes) in samples of 17 meningiomas. Genes that were found to be altered in those tumors were then sequenced in two additional groups of tumors.

Compared to most types of tumors, the researchers found, the meningiomas had fewer numbers of genetic changes or damage. In some of the tumors they found mutations in two genes that have roles in known cancer-causing signaling pathways. One, SMO, found in three tumors, is a member of the Hedgehog pathway. The second, AKT1, was discovered in five tumors and is a part of the PI3K-AKT-mTOR pathways that is implicated in breast, colorectal and lung cancers. A sixth tumor had a previously unknown mutation in the mTOR pathway.

Together, these mutant gene pathways appeared to be key drivers of 15 percent of the meningiomas studied. Experimental drugs that inhibit those abnormal pathways are in clinical trials and have shown promising activity, the researchers said, suggesting "that patients with these meningiomas may benefit from such targeted therapies already in development or use."

Co-first authors of the report are Priscilla Brastianos, MD, of Dana-Farber and Peleg Horowitz, MD, PhD, of Brigham and Women's Hospital. Other authors are at the Broad, Harvard Medical School, Brigham and Women's, and Massachusetts General Hospital. The research was supported by the Brain Science Foundation, the Pediatric Low-Grade Astrocytoma Foundation, and other foundations, the National Institutes of Health (K08 CA122833, K08 NS064168 and K12 CA090354-11), and the U.S. Department of Defense (W81XWH-12-1-0136.)


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Priscilla K Brastianos, Peleg M Horowitz, Sandro Santagata, Robert T Jones, Aaron McKenna, Gad Getz, Keith L Ligon, Emanuele Palescandolo, Paul Van Hummelen, Matthew D Ducar, Alina Raza, Ashwini Sunkavalli, Laura E MacConaill, Anat O Stemmer-Rachamimov, David N Louis, William C Hahn, Ian F Dunn, Rameen Beroukhim. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nature Genetics, 2013; DOI: 10.1038/ng.2526

Cite This Page:

Dana-Farber Cancer Institute. "Genomic sequencing identifies mutant 'drivers' of common brain tumor." ScienceDaily. ScienceDaily, 22 January 2013. <www.sciencedaily.com/releases/2013/01/130122162141.htm>.
Dana-Farber Cancer Institute. (2013, January 22). Genomic sequencing identifies mutant 'drivers' of common brain tumor. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2013/01/130122162141.htm
Dana-Farber Cancer Institute. "Genomic sequencing identifies mutant 'drivers' of common brain tumor." ScienceDaily. www.sciencedaily.com/releases/2013/01/130122162141.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
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:
from the past week

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