Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel gene mutations associated with bile duct cancer

19.01.2012
Mass. General Hospital Cancer Center findings could lead to targeted treatment for deadly tumor

Investigators at the Massachusetts General Hospital (MGH) Cancer Center have identified a new genetic signature associated with bile duct cancer, a usually deadly tumor for which effective treatment currently is limited.

Their report, which has been published online in The Oncologist, finds that growth-enhancing mutations in two related genes may account for nearly a quarter of bile duct tumors arising within the liver, presenting the possibility that drugs targeting this mutation could represent a new strategy to control tumor growth.

"Patients with bile duct cancer have a generally poor prognosis. Most of them are diagnosed with advanced or metastatic disease, so surgical resection is not feasible," says co-senior author Andrew Zhu, MD, PhD, director of Liver Cancer Research at the MGH Cancer Center. "Identifying this new and relatively common mutation in intrahepatic bile duct cancer may have significant implications for the diagnosis, prognosis and therapy of patients whose tumors harbor this mutation."

Cancers of the gallbladder and bile duct are diagnosed in 12,000 patients in the U.S. each year, the authors note; but only 10 percent are discovered early enough to allow successful surgical treatment. Chemotherapy is modestly effective, leading to an average survival time of less than one year.

The MGH Translational Research Laboratory was jointly established by the MGH Department of Pathology and the MGH Cancer Center to screen patient tumor samples for mutations known to drive tumor growth, identifying those that may be treatable with targeted therapies. As part of this project, the MGH team screened samples from 287 patients with gastrointestinal tumors for 130 known cancer-associated mutations and were surprised to find that 3 out of 12 biliary tract cancer tumors had mutations in a gene called IDH1. To confirm this finding, they ran a more detailed screen in additional samples, for a total of 62 bile duct tumors and 25 gallbladder tumors. Mutations in IDH1 were found in 13 percent of all bile duct tumors and in 23 percent of those located within the liver itself. Less commonly, mutations were identified in a similar gene IDH2.

"Mutations in these genes are rare examples of abnormalities that profoundly affect the normal function of a metabolic enzyme," says lead author Darrell Borger, PhD, co-director of the Translational Research Laboratory. "Our co-investigators previously found that, in other types of cancer, mutations in these genes cause overproduction and dramatic accumulation of the metabolite 2-hydroxyglutarate. How this causes tumor development is being actively investigated, and it is now emerging that 2-hydroxyglutarate can disrupt the activity of a family of proteins important in signal transduction and regulation of gene expression."

Although no approved drugs are currently available that target IDH mutations, extensive efforts are underway to develop such drugs, Zhu notes. "Identifying these mutations in bile duct cancer raises many questions, including whether mutational status can distinguish various types of bile duct tumors and help predict prognosis. Also of interest is determining whether high blood levels of 2-hydroxyglutarate could serve as a biomarker for IDH1/2 status, which could provide a minimally invasive way to monitor the effects of new IDH inhibitors that may become available," he says. Zhu is an associate professor, and Borger an instructor in Medicine at Harvard Medical School.

John Iafrate, MD, PhD, director of the Center for Integrated Diagnostics in MGH Pathology, is corresponding and co-senior author of the Oncologist paper. Additional co-authors are Kenneth Tanabe, MD, Kenneth Fan, Hector Lopez, Marek Ancukiewicz, PhD, Hannah Liebman, Eunice Kwak, MD, PhD, Jeffrey Clark, MD, David Ryan, MD, Vikram Deshpande, MBBS, Dora Dias-Santagata, PhD, and Leif Ellisen, MD, PhD, all of the MGH Cancer Center; Valeria Fantin, PhD, Kimberly Straley and David Schenkein, MD, Agios Pharmaceuticals; and Aram Hezel, MD, University of Rochester.

Massachusetts General Hospital (www.massgeneral.org), 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 $750 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.

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

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Superconducting vortices quantize ordinary metal

Russian researchers together with their French colleagues discovered that a genuine feature of superconductors -- quantum Abrikosov vortices of supercurrent -- can also exist in an ordinary nonsuperconducting metal put into contact with a superconductor. The observation of these vortices provides direct evidence of induced quantum coherence. The pioneering experimental observation was supported by a first-ever numerical model that describes the induced vortices in finer detail.

These fundamental results, published in the journal Nature Communications, enable a better understanding and description of the processes occurring at the...

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Rapid water formation in diffuse interstellar clouds

25.06.2018 | Physics and Astronomy

Using tree-fall patterns to calculate tornado wind speed

25.06.2018 | Earth Sciences

'Stealth' material hides hot objects from infrared eyes

25.06.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>