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.
Nature Genetics: http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.2405.html
Vanessa Wasta | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
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...
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...
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...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction