Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genome-wide scan maps mutations in deadly lung cancers; reveals embryonic gene link

06.09.2012
Scientists have completed a comprehensive map of genetic mutations linked to an aggressive and lethal type of lung cancer.

Among the errors found in small cell lung cancers, the team of scientists, including those at the Johns Hopkins Kimmel Cancer Center, found an alteration in a gene called SOX2 associated with early embryonic development.

"Small cell lung cancers are very aggressive. Most are found late, when the cancer has spread and typical survival is less than a year after diagnosis," says Charles Rudin, M.D., Ph.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center. "Our genomic studies may help identify genetic pathways responsible for the disease and give us new ideas on developing drugs to treat it."

The scientists found an increase in the copy number of the SOX2 gene in about 27 percent of small cell lung cancer samples. The resulting overproduction of proteins made by the SOX2 gene may play a role in igniting or sustaining abnormal cell growth in the lung. SOX2 offers a new target for scientists working to develop new drugs to combat this intractable cancer, say the investigators.

For the study, published online Sept. 2 in Nature Genetics, colleagues from Johns Hopkins, Genentech, the University of Texas Southwestern Medical Center and the University of Colorado Cancer Center scanned the genome's coding regions of 63 small cell lung cancers, including 42 with matching samples from patients' normal cells.

The scientific team scanned 56 of the samples for evidence of "amplification," a cellular process seen in cancer in which cancer cells acquire more than the typical two gene copies inherited from each parent. They found that one of the genes, SOX2, was amplified, in about 27 percent of the samples (15 of 56). SOX2 encodes a protein complex that binds to DNA and controls when and how genes are decoded to make other proteins. It has been linked to tissue and organ development in embryonic cells, and is one of the four genes used by scientists to convert adult cells into an embryonic state.

The scientists confirmed SOX2 amplification in an independent set of 110 small cell lung cancers. This amplification, they found, causes cells to overproduce SOX2 proteins and may promote growth that leads to cancer. Samples with amplified SOX2 also correlated with patients who had more advanced disease. "SOX2 is an important clue in finding new ways to treat small cell lung cancer," says Rudin. "We may be able to link a patient's outcome to this gene and develop a drug to target it or other genes it regulates." Rudin says his team will further explore the function of SOX2 and how to target it.

In addition to amplification, the study mapped errors in the genome's sequence and protein production levels.

In a second report appearing in the Sept. 2 issue of Nature Genetics, scientists from Germany and elsewhere completed another genome wide scan of small cell lung cancers and focused on changes in several genes, including FGFR1, a growth factor previously linked to cancer development. Rudin says FGFR1 may prove to be a rare but significant change among small cell lung cancers.

Funding support for the research came from the Burroughs Wellcome Fund, the Flight Attendant Medical Research Institute, the National Cancer Institute which is part of the National Institutes of Health (P50CA058184, P50CA70907, P50CA058187), the CAPES Foundation and Ministry of Education of Brazil.

Scientists contributing to the work include John T. Poirier, Emily A. Bergbower, James Shin, Peter B. Illei and Malcolm V. Brock from Johns Hopkins; Steffen Durinck, Eric W. Stawiski, Zora Modrusan, David S. Shames, Yinghui Guan, Joseph Guillory, Celina Sanchez Rivers, Catherine K. Foo, Deepali Bhatt, Jeremy Stinson, Florian Gnad, Peter M. Haverty, Robert Gentleman, Subhra Chaudhuri, Vasantharajan Janakiraman, Bijay S. Jaiswal, Chaitali Parikh, Wenlin Yuan, Zemin Zhang, Hartmut Koeppen, Thomas D. Wu, Howard M. Stern, Robert L. Yauch, Frederic J. de Sauvage, Richard Bourgon and Somasekar Seshagiri from Genentech; Kenneth E. Huffman, Adi F. Gazdar and John D. Minna from the University of Texas Southwestern Medical Center; and Diego D. Paskulin and Marileila Varella-Garcia from the University of Colorado Cancer Center.

Rudin has previously consulted for Genentech. Illei is a consultant for Leica Microsystems, manufacturer of a device used in this study. The terms of these arrangements are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

More information:

Nature Genetics: http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.2405.html

Vanessa Wasta | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>