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.)
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter: @danafarber or Facebook: facebook.com/danafarbercancerinstitute.
Bill Schaller | EurekAlert!
Researchers invent tiny, light-powered wires to modulate brain's electrical signals
21.02.2018 | University of Chicago
The “Holy Grail” of peptide chemistry: Making peptide active agents available orally
21.02.2018 | Technische Universität München
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
21.02.2018 | Life Sciences
21.02.2018 | Life Sciences
21.02.2018 | Materials Sciences