Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover new genetic anomalies in lung cancer

22.12.2014

Number of fusions in a tumor linked to more aggressive cancer

Developing effective treatments for lung cancer has been challenging, in part because so many genetic mutations play a role in the disease.


This is Arul Chinnaiyan, M.D., Ph.D.

Credit: University of Michigan Comprehensive Cancer Center

By analyzing the DNA and RNA of lung cancers, researchers at the University of Michigan Comprehensive Cancer Center found that patients whose tumors contained a large number of gene fusions had worse outcomes than patients with fewer gene fusions. Gene fusions are a type of genetic anomaly found in cancers that occurs when genes get rearranged and fuse together.

In addition, the researchers identified several new genetic anomalies that occur in lung cancer, including in patients with a history of smoking.

"Lung cancer is quite a complex disease with many causes. Our deep sequencing analysis found new gene fusions in lung cancers that were negative for the most commonly known fusions. These new anomalies could potentially be targets for developing new treatments," says study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the University of Michigan Medical School.

The study looked at 753 lung cancer samples that represented both smokers and non-smokers. The first 153 samples came from the University of Michigan and were combined with 521 samples from a report published by The Cancer Genome Atlas.

The researchers found 6,348 unique fusions with an average of 13 fusions per tumor sample. Anomalies in two gene pathways were most prevalent: the Hippo pathway, which has previously been linked to some rare cancers, and NRG1, which has not previously been seen in cancer.

The study appears in Nature Communications.

Researchers know that three common gene fusions - involving ALK, RET and ROS - play a role in about 5 percent of lung cancers, but primarily in non-smokers. The new anomalies were found only in patients who did not have ALK, RET or ROS fusions.

"Our results indicate that in the more genomically complex smoking-related lung cancers, gene fusion events appear to be frequent," says study author David G. Beer, Ph.D., John and Carla Klein Professor of Thoracic Surgery and professor of Radiation Oncology at the University of Michigan Medical School and co-director of Cancer Genetics at the U-M Comprehensive Cancer Center.

Drug companies are already investigating drugs that could target the Hippo pathway and NRG1. The research team suggests exploring these inhibitors as potential therapeutics in lung cancer.

In addition, the finding that the number of gene fusions was tied to prognosis suggests that a screen could be developed to help doctors determine how aggressive a patient's tumor is likely to be - and to tailor treatment accordingly.

The study identified many different gene fusions that comprise the landscape of lung cancer, with most occurring in only a small number of individual tumor samples. The Hippo pathway fusions were present in 3 percent of patients and NRG1 fusions in 4 percent. The researchers suggest expanding lung cancer subtypes based on these molecular characteristics.

"We've previously had success in targeting therapies against low-recurrence gene fusions. Large-scale genome analyses like this allow us to identify more of the key drivers of each patient's tumor so that we can match the most appropriate therapies," Chinnaiyan says.

Additional authors: Saravana M. Dhanasekaran, O. Alejandro Balbin, Guoan Chen, Ernest Nadal, Shanker Kalyana-Sundaram, Jincheng Pan, Brendan Veeneman, Xuhong Cao, Rohit Malik, Pankaj Vats, Rui Wang, Stephanie Huang, Jinjie Zhong, Xiaojun Jing, Matthew Iyer, Yi-Mi Wu, Paul W. Harms, Jules Lin, Rishindra Reddy, Christine Brennan, Nallasivam Palanisamy, Andrew C. Chang, Anna Truini, Mauro Truini, Dan R. Robinson

Funding: National Cancer Institute grants R01 CA154365, P30 CA46592, F31 CA165866, T32 CA140044; Dermatology Foundation; Spanish Society of Medical Oncology Fellowship; China Scholarship Council Award; National Science Foundation grant 0903629

Disclosure: None

Reference: Nature Communications, doi: 10.1038/ncomms6893, Dec. 22, 2014

Resources:
U-M Cancer AnswerLine, 800-865-1125

U-M Comprehensive Cancer Center, http://www.mcancer.org

Clinical trials at U-M, http://www.mcancer.org/clinicaltrials

mCancerTalk blog, http://uofmhealthblogs.org/cancer

Media Contact

Nicole Fawcett
nfawcett@umich.edu
734-764-2220

@UMHealthSystem

http://www.med.umich.edu

Nicole Fawcett | EurekAlert!

More articles from Life Sciences:

nachricht Helping to Transport Proteins Inside the Cell
21.11.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht UNH researchers create a more effective hydrogel for healing wounds
21.11.2018 | University of New Hampshire

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First diode for magnetic fields

Innsbruck quantum physicists have constructed a diode for magnetic fields and then tested it in the laboratory. The device, developed by the research groups led by the theorist Oriol Romero-Isart and the experimental physicist Gerhard Kirchmair, could open up a number of new applications.

Electric diodes are essential electronic components that conduct electricity in one direction but prevent conduction in the opposite one. They are found at the...

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Helping to Transport Proteins Inside the Cell

21.11.2018 | Life Sciences

Meta-surface corrects for chromatic aberrations across all kinds of lenses

21.11.2018 | Power and Electrical Engineering

Removing toxic mercury from contaminated water

21.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>