Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene in eye melanomas linked to good prognosis

17.01.2013
Melanomas that develop in the eye often are fatal. Now, scientists at Washington University School of Medicine in St. Louis report they have identified a mutated gene in melanoma tumors of the eye that appears to predict a good outcome.

The research is published in the advance online edition of Nature Genetics.

“We found mutations in a gene called SF3B1,” says senior author Anne Bowcock, PhD, professor of genetics. “The good news is that these mutations develop in a distinct subtype of melanomas in the eye that are unlikely to spread and become deadly.”

Eye tumors called uveal melanomas occur in about 2,000 patients a year, making up about 5 percent of all melanomas. In many patients, there are no symptoms, and the tumors become fatal when they spread to the liver.

Several years ago, Bowcock and the study’s lead author, J. William Harbour, MD, a former Washington University eye surgeon who is now at the University of Miami, identified a commonly mutated gene, BAP1, in patients with uveal melanomas.

They found BAP1 alterations in about 80 percent of uveal melanomas with a poor prognosis, called class II tumors. About 75 percent of patients with these tumors die within five years, a sharp contrast to the generally favorable outcomes of patients whose tumors don’t have BAP1 mutations, called class I.

For the new study, Bowcock and her colleagues initially sequenced the DNA of uveal melanomas from 18 patients whose BAP1 status was already known. Seven had no BAP1 mutations (class I tumors), and 11 had BAP1 mutations (class II tumors).

The researchers’ analysis uncovered alterations in the SF3B1 gene in three of the patients.

“This is the first time mutations in this gene have been found in uveal melanoma,” says Bowcock, who also is a professor of pediatrics and of medicine.

As part of the current study, the researchers also looked for SF3B1 mutations in uveal melanoma tumors from 102 patients, finding it in nearly 20 percent of them. Mutations in the gene were linked to favorable features, including a younger age at diagnosis and a far lower metastasis rate.

Interestingly, SF3B1 mutations always occurred at the same site of the gene. And the SF3B1 and BAP1 mutations were found to be almost mutually exclusive, meaning that if patients had a mutation in one of the genes, they were unlikely to have a mutation in the other.

“This suggests mutations in these genes may represent alternative pathways in tumor progression,” Bowcock says.

The SF3B1 gene also has been reported recently by other researchers to be mutated in a pre-leukemia illness called myelodysplastic syndrome. For these patients, SF3B1 mutations mean the condition is less likely to develop into a full-blown leukemia. Changes in the SF3B1 gene also have been found in chronic lymphocytic leukemia and less frequently in breast cancer and other solid tumors. The gene’s link to prognosis is unclear for these cancers.

Normally, the SF3B1 gene is involved in converting DNA’s chemical cousin, RNA, into messenger RNA. This messenger molecule carries DNA’s code and serves as a template for making proteins. The researchers don’t yet understand how mutations in this gene are involved in cancer but it’s the next step of their research.

“We want to understand the functional consequences of mutations in SF3B1,” Bowcock says. “How are changes in this gene linked to cancer development? This is the fourth gene known to be mutated in uveal melanoma along with BAP1 and the genes GNAQ and GNA11. A complete understanding of the molecular basis of this tumor will be invaluable in predicting prognosis and in the identification and development of novel treatments for this cancer.”

Harbour JW, Roberson EDO, Anbunathan H, Onken MD, Worley LA, Bowcock AM. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nature Genetics. Jan. 14, 2012.

The research is supported by grants from the National Institutes of Health (NIH) (R01 CA16187001 and CA12597007), the Melanoma Research Alliance, the Melanoma Research Foundation, the Tumori Foundation , Research to Prevent Blindness, Inc., and awards to the Department of Ophthalmology and Visual Sciences at Washington University from a Research to Prevent Blindness, Inc., unrestricted grant and also the NIH Vision Core grant (P30 EY02687c) and an NIH training grant (5 T32 AR007279-32).

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Caroline Arbanas | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria

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 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....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

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

Microscopic trampoline may help create networks of quantum computers

17.07.2018 | Information Technology

In borophene, boundaries are no barrier

17.07.2018 | Materials Sciences

The role of Sodium for the Enhancement of Solar Cells

17.07.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>