Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New knowledge of genes driving bladder cancer points to targeted treatments

15.09.2014

The story of cancer care seems so simple: find the mutated gene that causes cancer and turn it off or fix it. But rarely does a single gene cause cancer.

More often, many genes are altered together to drive the disease. So the challenge becomes sorting out which altered genes are the most to blame in which cancers. A collaborative study between researchers at the University of Colorado Cancer Center and the National Cancer Institute (NCI) published today in the journal Clinical Cancer Research takes an important step toward answering this question in bladder cancer.


Dan Theodorescu, M.D., Ph.D., director of the University of Colorado Cancer Center, and colleagues from the National Cancer Institute show genes commonly mutated in bladder cancer, implying at least two distinct genotypes and phenotypes for the disease.

Credit: CU Cancer Center

Specifically, the study examined a mutation-rich layer of the genome called the exome of 54 bladder tumors from primarily Caucasian patients. The study is the first to show alterations in the gene BAP1 in 15 percent of tumors; the gene is a likely tumor suppressor and so bladder cancers with alterations in this gene may be without an important check on the growth and survival of bladder cancer tissue.

Somatic BAP1 alterations contribute to a high frequency of tumors (10/14, 71 percent) with defects in genes encoding BRCA1 and BRCA2 pathway proteins, pathways that have been previously implicated in breast and other cancer types.

More surprising, a second, highly independent genetic pathway was found in 69 percent of 54 tumors, in which alterations of the TERT promoter created what is effectively a second subset of bladder cancer. The TERT promoter mutations did not significantly correlate with somatic alterations in other cancer genes, indicating that this alteration confers a presumed oncogenic benefit independent of other cancer gene alterations.

The gene KDM6A was frequently altered in 24 percent of tumors, and the study shows that experimental depletion in of KDM6A in human bladder cancer cells enhanced in vitro proliferation, in vivo tumor growth, and cell migration, confirming its role as a cancer driver and tumor suppressor in bladder tissue.

The study revealed other surprising relationships between the types of genetic alterations in bladder tumors. BAP1 somatic mutations may correlate with papillary features in some bladder tumors and were significantly more frequent in Caucasian patients than Chinese patients, indicating ethnicity, lifestyle, or exposure may influence somatic BAP1 mutations.

BAP1 and KDM6A mutations significantly co-occurred in tumors, indicating they likely supply mutually reinforcing survival advantages to cancer cells. Finally, just four genes encoding chromatin remodeling enzymes, BAP1, KDM6A, ARID1A, and STAG2, were altered in 46 percent of 54 tumors and demonstrate a major contribution from somatic alterations targeting chromatin remodeling functions in bladder cancer.

"Taken together, we have identified new subtypes of bladder cancer that are related by somatic and germline genetic alterations that are observed in patient tumors. These subtypes may be vulnerable to subtype-specific therapeutic targeting. For example, many tumors in this study possessed cells with mutations targeting the BRCA DNA repair pathway indicating they are likely to be deficient in their ability to repair DNA," says Dan Theodorescu, MD, PhD, professor of Urology and Pharmacology, director of the University of Colorado Cancer Center and the paper's senior author.

"Thus the tumor cells should be especially sensitive to chemotherapeutic drugs that create DNA damage. This is an excellent example of a case in which basic science can now suggest targeted treatments that have the real possibility to benefit patients," says Michael Nickerson PhD, staff scientist and lead author from the National Cancer Institute.

###

Located on the Anschutz Medical Campus, the University of Colorado Cancer Center is Colorado's only National Cancer Institute-designated comprehensive cancer center, a distinction recognizing its outstanding contributions to research, clinical trials, prevention and cancer control. CU Cancer Center is a member of the prestigious National Comprehensive Cancer Network®, an alliance of the nation's leading cancer centers working to establish and deliver guidelines for clinical cancer practice. Our primary clinical care partner, the University of Colorado Hospital, was recently ranked #15 for cancer care by U.S. News & World Report. CU Cancer Center is comprised of more than 350 researchers and physicians at three state universities and other institutions, all working toward one goal: Translating cancer science into life. For more information visit Coloradocancercenter.org and follow CU Cancer Center on Facebook and Twitter.

Garth Sundem | Eurek Alert!

Further reports about: BAP1 Cancer DNA alterations genes mutations pathway somatic treatments tumors

More articles from Health and Medicine:

nachricht World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern

nachricht Therapy of preterm birth in sight?
19.07.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>