Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutation discovery may improve treatment for rare brain tumor type

13.01.2014
Study findings could lead to targeted therapies for hard-to-treat craniopharyngiomas

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.

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.

Santagata, a pathologist, is affiliated with Dana-Farber/Boston Children's, Brigham and Women's Hospital and Harvard Medical School (HMS). Co-senior authors of the study are Mark Kieran, MD, PhD, of Dana-Farber/Boston Children's and HMS; and Gad Getz, PhD, of the Broad Institute, Massachusetts General Hospital (MGH) and HMS.

The study has three co-first authors: Brastianos of MGH, Dana-Farber Cancer Institute, HMS and the Broad; Amaro Taylor-Weiner of the Broad; and Peter Manley, MD, of Dana-Farber/Boston Children's.

The research was supported by Pedals for Pediatrics and the Clark family.

The Dana-Farber/Boston Children's Cancer and Blood Disorders Center brings together two internationally known research and teaching institutions that have provided comprehensive care for pediatric oncology and hematology patients since 1947. The Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Children's Hospital and outpatient care at the Dana-Farber Cancer Institute's Jimmy Fund Clinic. Dana-Farber/Boston Children's brings the results of its pioneering research and clinical trials to patients' bedsides through five clinical centers: the Blood Disorders Center, the Brain Tumor Center, the Hematologic Malignancies Center, the Solid Tumors Center, and the Stem Cell Transplant Center.

Irene Sege | EurekAlert!
Further information:
http://www.dana-farber.org/

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>