Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NIH study reveals new genetic culprit in deadly skin cancer

01.09.2009
Sequencing work points to new target for melanoma treatment

Drawing on the power of DNA sequencing, National Institutes of Health researchers have identified a new group of genetic mutations involved in the deadliest form of skin cancer, melanoma. This discovery is particularly encouraging because some of the mutations, which were found in nearly one-fifth of melanoma cases, reside in a gene already targeted by a drug approved for certain types of breast cancer.

In the United States and many other nations, melanoma is becoming increasingly more common. A major cause of melanoma is thought to be sun exposure; the ultraviolet radiation in sunlight can damage DNA and lead to cancer-causing genetic changes within skin cells.

In work published in the September issue of Nature Genetics, a team led by Yardena Samuels, Ph.D., of the National Human Genome Research Institute (NHGRI) sequenced the protein tyrosine kinase (PTK) gene family in tumor and blood samples from people with metastatic melanoma. The samples were collected by the study's coauthor Steven Rosenberg, M.D., Ph.D., a leading expert on melanoma and chief of surgery at the National Cancer Institute (NCI).

The PTK family includes many genes that, when mutated, promote various types of cancer. However, relatively little had been known about roles played by PTK genes in human melanoma. The NIH study was among the first to use large-scale DNA sequencing to systematically analyze all 86 members of the PTK gene family in melanoma samples.

The team's initial survey, which involved samples from 29 melanoma patients, identified mutations in functionally important regions of 19 PTK genes, only three of which had been previously implicated in melanoma. The researchers then conducted more detailed analyses of those 19 genes in samples from a total of 79 melanoma patients.

One of the newly implicated genes stood out from the rest. Researchers detected mutations in the ERBB4 gene (also known as HER4) in 19 percent of patients' tumors, making it by far the most frequently mutated PTK gene in melanoma. In addition, researchers found that many ERBB4 mutations were located in functionally important areas similar to those seen in other PTK oncogenes involved in lung cancer, brain cancer and gastric cancer.

Next, the researchers moved on to laboratory studies of melanoma cells with ERBB4 mutations. They found that these melanoma cells were dependent on the presence of mutant ERBB4 for their growth. What's more, the melanoma cells grew much more slowly when they were exposed to a chemotherapeutic drug known to inhibit ERBB4. The drug, called lapatinib (Tykerb), was approved by the Food and Drug Administration in 2007 for combination use in breast cancer patients already taking the drug capecitabine (Xeloda).

Encouraged by their study results, the researchers are planning a clinical trial using lapatinib in patients with metastatic melanoma harboring ERBB4 mutations. The clinical trial will be conducted under the direction of Dr. Rosenberg at the NIH Clinical Center. "This collaborative study represents an ideal example of how sophisticated genetic analyses can be translated to the benefit of cancer patients," said Dr. Rosenberg.

"We have found what appears to be an Achilles' heel of a sizable share of melanomas," said Dr. Samuels, who is an investigator in the Cancer Genetics Branch of the NHGRI's Division of Intramural Research. "Though additional work is needed to gain a more complete understanding of these genetic mutations and their roles in cancer biology, our findings open the door to pursuing specific therapies that may prove useful for the treatment of melanoma with ERBB4 mutations."

In addition to ERBB4, the researchers identified two additional PTK genes, FLT1 and PTK2B, with a relatively high rate of mutations in melanoma. Each of these genes was mutated in about 10 percent of the tumor samples studied.

NHGRI Scientific Director Eric D. Green, M.D., Ph.D., pointed out how such research is helping to lay the groundwork for the era of personalized medicine. "We envision a day when each cancer patient will have therapies tailored to the specific genetic profile of his or her tumor. Ultimately, this should lead to more effective and less toxic approaches to cancer care," said Dr. Green, who directs the NIH Intramural Sequencing Center, which generated the DNA sequence data for the melanoma study.

In addition to NIH scientists, the team included a researcher from the Johns Hopkins Kimmel Cancer Center in Baltimore.

In May 2009, Dr. Samuel's group reported in Nature Genetics another large-scale DNA sequencing study of a different group of genes involved in melanoma, the matrix metalloproteinase (MMP) gene family. This earlier study found that one gene, MMP-8, thought to spur cancerous growth actually served to inhibit it. Those findings are now helping to shape melanoma treatment strategies aimed at MMP genes.

For high resolution micrographs of metastatic melanoma, go to http://www.genome.gov/pressDisplay.cfm?photoID=20152 and http://www.genome.gov/pressDisplay.cfm?photoID=20153.

NHGRI is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at its Web site, www.genome.gov.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health — "The Nation's Medical Research Agency" — includes 27 institutes and centers, and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases.

Geoffrey Spencer | EurekAlert!
Further information:
http://www.nih.gov

More articles from Life Sciences:

nachricht Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht Identified the component that allows a lethal bacteria to spread resistance to antibiotics
27.07.2017 | Institute for Research in Biomedicine (IRB Barcelona)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | 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

 
Latest News

Programming cells with computer-like logic

27.07.2017 | Life Sciences

Identified the component that allows a lethal bacteria to spread resistance to antibiotics

27.07.2017 | Life Sciences

Malaria Already Endemic in the Mediterranean by the Roman Period

27.07.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>