Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fish Shed Light on Human Melanoma

19.06.2012
A transparent member of the minnow family is providing researchers at Weill Cornell Medical College in New York City with insight into human melanoma – a form of skin cancer – that may lead to new or repurposed drug treatments, for skin and other cancers.

The experiments will be reported at the “Model Organisms to Human Biology: Cancer Genetics” Meeting, June 17-20, 2012, at the Omni Shoreham Hotel in Washington, D.C., which is sponsored by the Genetics Society of America.

The meeting will bring together investigators who study cancer-relevant biology in model organisms — such as fruit flies, yeast, fungi, worms, and mice — with investigators studying human cancer. Each session includes both speakers from the model organism research community and those focusing on human cancer research.

Each year in the United States, 8,700 people die from malignant melanoma. Yariv Houvras, MD, PhD, at Weill Cornell Medical College and Craig Ceol, PhD, at the University of Massachusetts Medical School, along with their colleagues, discovered that a previously-identified human gene, SETDB1, accelerated the progression of cancer when a copy of the gene was inserted into the zebrafish genome. This led researchers to believe that this gene may have a similar effect in humans. In fish with the human SETDB1 gene, melanomas appear earlier and spread faster, which is easily seen through the transparent skin of the zebrafish.

Zebrafish are valuable models for people. Their generation time is three to four months, and each female lays hundreds of eggs every two to three days. In addition, researchers can easily manipulate its genes, many of which have human counterparts, and they can even see inside the developing embryos because they are transparent.

In the work that will be presented at the meeting on Monday, June 18, the researchers used the fish to probe a part of human chromosome 1 that is involved in melanoma. In humans, cancer gets underway when a sequence of genes mutate, including a key gene called BRAF. About 60 percent of human melanomas have a specific BRAF mutation, and a drug targeting mutant BRAF, Vemurafenib, was approved by the Food and Drug Administration (FDA) last year for the treatment of patients with metastatic melanoma. It’s not unusual for cancers to have multiple genetic mutations, so the researchers reasoned that additional genes found in the amplified region on chromosome 1 could also drive melanoma.

And that’s where the zebrafish came in. The researchers delivered SETDB1 into single-cell zebrafish embryos that already had BRAF mutations, and the resulting adult fish had the human gene in every melanocyte. They discovered that SETDB1 is a master regulator, playing an important role in the regulation of many other genes and accelerating the cancer. SETBD1 acts by altering regions of the genome using a biochemical process called methylation, and in doing so prevents many genes from being turned on and making their appropriate protein products.

Methylation of chromatin is an epigenetic change – that is, it doesn’t alter the underlying DNA sequence. SETDB1 acts by binding to DNA and changing the methylation pattern, which it does at several thousand places in the human genome, according to the studies performed by Dr. Houvras and colleagues.

“This is a very exciting area. Many new connections are being made between chromatin-modifying enzymes and cancer,” Dr. Houvras explains. The FDA has already approved a drug that inhibits DNA methylation, Decitabine, for a blood disorder called myelodysplasia. “Within the next few years drugs that inhibit histone methylation will be tested in clinical trials. These drugs may target SETDB1 and other histone methyltransferases and help treat specific cancers that rely on these pathways,” Dr. Houvras notes.

The zebrafish may be easy to work with, however this project was anything but. The researchers scaled up their experiments to follow several thousand fish for six months. They performed over 35,000 individual observations, Dr. Houvras says, as they watched fish develop melanomas individually.

The role of SETDB1 in the cancer isn’t black-and-white. In humans it’s highly expressed in 5 percent of normal melanocytes, in 15 percent of benign nevi, and in 70 percent of malignant melanomas. Moles that overexpress the gene may be more likely to progress to cancer, the researchers speculate – which could be very useful information, and all thanks to the zebrafish.

ABOUT THE MODEL ORGANISMS TO HUMAN BIOLOGY MEETING: The GSA MOHB Meeting has been held every other year since 2006. The GSA Board developed this meeting to enable basic research scientists studying genetic diseases in model organisms and scientists studying these diseases in humans to have a forum for discussion of their findings and to forge collaborative investigations.

ABOUT GSA: Founded in 1931, the Genetics Society of America (GSA) is the professional membership organization for scientific researchers, educators, bioengineers, bioinformaticians and others interested in the field of genetics. Its nearly 5,000 members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level. GSA is dedicated to promoting research in genetics and to facilitating communication among geneticists worldwide through its conferences, including the biennial conference on Model Organisms to Human Biology, an interdisciplinary meeting on current and cutting edge topics in genetics research, as well as annual and biennial meetings that focus on the genetics of particular organisms, including C. elegans, Drosophila, fungi, mice, yeast, and zebrafish. GSA publishes GENETICS, a leading journal in the field and an online, open-access journal, G3: Genes|Genomes|Genetics. For more information about GSA, please visit www.genetics-gsa.org. Also follow GSA on Facebook at facebook.com/GeneticsGSA and on Twitter @GeneticsGSA.

Phyllis Edelman | Newswise Science News
Further information:
http://www.genetics-gsa.org

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

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

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | 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

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>