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
Reference: Nature Communications, doi: 10.1038/ncomms6893, Dec. 22, 2014
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
Nicole Fawcett | EurekAlert!
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences