Genomic sequencing identifies mutant 'drivers' of common brain tumor
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."
Journal reference: Nature Genetics
Provided by Dana-Farber Cancer Institute
- Why do meningiomas grow during pregnancy? Nov 20, 2012 | not rated yet | 0
- Genetic link to rare brain tumour discovered Aug 02, 2011 | not rated yet | 0
- Melanoma: Whole-genome sequencing of 25 tumors confirms role of sun damage, reveals new genetic alterations May 09, 2012 | not rated yet | 0
- Definition of lung squamous cell carcinoma genome opens doors to better, more targeted therapies Sep 09, 2012 | not rated yet | 0
- Scientists identify overactive genes in aggressive breast cancers Jun 01, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics 11 hours ago | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
A Nobel prize-winning scientist Tuesday played down "shock-horror scenarios" that a new virus strain will emerge with the potential to kill millions of people.
5 minutes ago | not rated yet | 0
(AP)—The decade-old law that transformed the battle against HIV and AIDS in developing countries is at a crossroads. The dream of future generations freed from the epidemic is running up against an era ...
50 minutes ago | not rated yet | 0
Johns Hopkins researchers say they have discovered specific chemical alterations in two genes that, when present during pregnancy, reliably predict whether a woman will develop postpartum depression.
1 hour ago | not rated yet | 0 |
Children who have suffered maltreatment are 36% more likely to be obese in adulthood compared to non-maltreated children, according to a new study by King's College London. The authors estimate that the prevention or effective ...
1 hour ago | not rated yet | 0
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
10 hours ago | 4.6 / 5 (13) | 4 |
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
13 hours ago | 4.8 / 5 (12) | 2 |