"The fact that the defective genes code for metabolic enzymes found only in malignant glioma, and not in normal tissue, could make the gene products therapeutic targets," says Hai Yan, M.D., Ph.D., lead author, an assistant professor in the Duke Department of Pathology. The findings are published in the Feb. 19 issue of the New England Journal of Medicine.
These genetic flaws might also help distinguish between primary and secondary glioblastoma multiforme (GBM), two subtypes of especially deadly malignant gliomas, with survival of only months after their diagnosis. Patients that have mutation of the genes, isocitrate dehydrogenase 1, gene 1 and 2 (IDH1 and IDH2), also had a longer survival time.
Because the researchers found this genetic mutation in several different stages of glioma development, "the results suggested that the IDH mutations are the earliest genetic changes that start glioma progression," said Darell Bigner, M.D., Ph.D., a co-author and director of the Preston Robert Tisch Brain Tumor Center at Duke University. Yet, patients with GBM or anaplastic astrocytoma who had the IDH mutations also were found to live longer than patients with those two cancers who lacked the mutations.
Malignant glioma appears to be two diseases, one that involves IDH mutations and one that doesn't, Yan explained. "As a cancer culprit gene, IDH mutations do contribute to cancer," he said. "Meanwhile, patients with the IDH mutation live longer with their cancer. The IDH mutation could serve as a biomarker that would help single out individuals who are likely to have better outcomes and receive different treatment."
He said that IDH mutations appear to define a specific subtype of GBMs, which is important so that physicians can plan specific treatment strategies to target this specific subtype of GBMs. "All GBMs are basically considered the same and are treated in the same way," Yan said. "Our studies clearly demonstrate that we need to start thinking about them as different. It is entirely possible that treatments that work for the IDH-mutation subtype would not work for the rest of GBMs, or vice versa." Knowing the tumor subtype has significant implications for how we plan future clinical trials for patients with GBMs, he added.
"I can say this is potentially one of the most important discoveries in genetic studies on malignant gliomas, in the low-grade to high-grade forms of the tumor," Yan said. "The results are so clear cut. I have been doing intensive genetic studies in brain cancers for six years, and I have never seen gene mutations as striking as in this study."
The researchers found IDH1 mutations in more than 70 percent of astrocytomas and olidgodendrogliomas (WHO grade II and III), as well as in secondary GBMs (WHO grade IV). Those without the IDH1 mutation had similar mutations in the closely related IDH2 gene. The mutations decreased IDH enzymatic activity. This signaled that IDH mutations are likely important in initiating malignant gliomas, but it is not known yet how they contribute to glioma development.
The findings are important in many ways. IDH can be used to distinguish primary GBMs, which do not arise from an existing tumor, from secondary GBMs, which arise from low-grade glioma tumors. The IDH1 mutation is missing in pilocytic astrocytomas, which means these particular brain tumors arise through a different mechanism.
Mary Jane Gore | EurekAlert!
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy