Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Multi-institutional team finds targetable mutation in rare brain tumor

13.01.2014
BRAF mutation associated with other cancers appears to drive papillary craniopharyngiomas

A team led by investigators from Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH) and the Broad Institute has found that a gene mutation associated with several types of cancer also may be responsible for a rare but debilitating brain tumor called papillary craniopharyngioma. Their discovery, reported online in Nature Genetics, could lead to new therapies for this currently hard-to-treat tumor.

"We were delighted to find that the same BRAF mutation previously described in melanomas and other brain tumors appears to be driving the growth of these tumors," says Priscilla Brastianos, MD, of the MGH Cancer Center and the Broad Institute, co-corresponding author of the report. "BRAF inhibitors have shown great promise in treating patients with other tumors with this mutation, and we hope to quickly evaluate these drugs in patients with papillary craniopharyngioma in hopes of reducing the serious consequences of this disease."

Craniopharyngiomas arise at the base of the skull adjacent to the pituitary gland, the hypothalamus and other critical brain structures. Although they are not inherently aggressive tumors, because of their location they can significantly compromise vision and other neurologic and endocrine functions. The tumors cling to brain structures, usually making surgical removal challenging, and radiation therapy can cause vascular abnormalities or other tumors.

There are two subtypes of craniopharyngiomas – adamantinomatous tumors, which are more common in children, and papillary tumors, usually seen in adults. Recent studies have associated mutations in an oncogene called CTNNB1 with adamantinomatous tumors, but prior to this study, no information was available about the molecular drivers of the papillary subtype.

In their search for possible mutations associated with papillary tumors, the research team first performed whole exome sequencing of 15 craniopharyngiomas – 12 adamantinomatous and 3 papillary. Among adamantinomatous tumors the previously identified CTNNB1 mutation was found in 11 of the 12 samples; and for the first time, the known tumor-associated BRAF mutation was identified in all three papillary tumors.

The researchers followed that finding with a targeted genotyping of tumor samples from an additional 95 patients. Among tested papillary tumors, 94 percent had the BRAF mutation, while 96 percent of the adamantinomatous tumors had the CTNNB1 mutation. The investigators also confirmed that both types of tumors had very few other mutations and that the BRAF or CTNNB1 mutations were present in all tumor cells, suggesting they occurred early in tumor development.

"There are currently no medical therapies available for craniopharyngiomas, but potent compounds that block BRAF signaling are in hand. So we are very hopeful that these targeted therapies can drastically alter the management of these tumors," says Sandro Santagata, MD, PhD, BWH Department of Pathology and a co-corresponding author of the Nature Genetics paper. "Inhibitors of the signaling pathway controlled by CTNNB1 that are currently in clinical trials should be investigated for adamantinomatous tumors, and we're planning to evaluate the BRAF inhibitors that have had promising results against melanoma for treatment of papillary craniopharyngiomas."

Santagata is an assistant professor of Pathology, and Brastianos is an instructor in Medicine at Harvard Medical School. Along with Brastianos, the co-lead authors of the report are Amaro Taylor-Weiner, Broad Institute, and Peter Manley, MD, Dana-Farber Cancer Institute; Mark Kieran, MD, PhD, DFCI and Gad Getz, PhD, MGH Pathology and Broad Institute, are co-senior authors. David Louis, MD, chief of MGH Pathology, also made significant contributions to the study, as did additional collaborators from MGH, BWH, DFCI, Johns Hopkins University, the University of Pennsylvania, and other institutions. Support for the study includes grants from Pedals for Pediatrics and the Jared Branfman Sunflowers for Life Foundation for Pediatric Brain and Spinal Cord Research.

Brigham and Women's Hospital is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH is an international leader in basic, clinical and translational research on human diseases, and has more than 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $650 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health among independent hospitals.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

The Eli and Edythe L. Broad Institute of Harvard and MIT was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community. The Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide.

Katie Marquedant | EurekAlert!
Further information:
http://www.massgeneral.org/

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>