Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inherited gene change also found in spontaneous tumors

10.10.2005


New research shows that a small gene variation that increases the risk of inherited cancer can also arise during the development of spontaneous, or non-inherited, tumors.



The findings, published in the Oct. 5 issue of the Journal of the American Medical Association, suggest that the variation might play a fundamental role in the development and spread of cancer in the body, and that the variant could be an important target for anticancer drugs.

The research focused on the gene for type 1 transforming growth factor-beta receptor, or TGFBR1, and on a variation of that gene, TGFBR1-6A. The 6A variant can be inherited and can increase cancer susceptibility by 19 percent in individuals with one copy of the gene and by 70 percent in those carrying two copies.


The study showed that the 6A variant, which is carried by nearly one in seven Americans generally and by one in six people with cancer, can also arise as a gene mutation during cancer development.

The research was led by scientists at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University .

“Our findings show for the first time that the 6A variation of this gene also arises by mutation during tumor development in patients born with the normal TGFBR1 gene, and that this mutation may contribute to tumor growth and spread,” says principal investigator Christopher M. Weghorst, an associate professor with the OSU School of Public Health and a researcher with the Comprehensive Cancer Center.

Furthermore, the researchers found the 6A variant in half of the metastatic liver tumors they examined. These tumors had spread to the liver from the colon.

In some cases, the variants in these tumors had been inherited, but, says lead author Boris Pasche, assistant professor of medicine at Northwestern University , “the majority of the liver metastases had acquired the variant as a mutation during cancer progression. This shows the dramatic impact of this gene on the growth of cancer cells in humans, and suggests that this molecule may become an excellent target for new therapies for patients with colorectal cancer, especially those with liver metastases.”

The findings also provide insights into the effects of the signaling molecule transforming growth factor beta. Transforming growth factor beta normally slows the growth of cells known as epithelial cells, and may stimulate the growth of cancerous epithelial cells. (Epithelial cells line the ducts, passages and hollow organs of the body and are the cells in which most cancers arise.)

This signaling molecule works by docking with TGFBR1, which is located on the surface of cells. Normally, the joining of the two molecules tells the cell to stop growing.

This new research indicates, however, that if the normal TGFBR1 gene mutates, causing a cell to have the TGFBR1-6A variant on its surface, the signaling molecule enables the cell to start growing and helps the growing tumor to metastasize.

For this study, Weghorst, Pasche and a group of colleagues looked for the 6A gene variation in tumor tissue from 226 patients with head and neck cancer, 157 patients with primary colorectal cancer, 104 patients with breast cancer and 44 patients with liver metastases from colorectal cancer.

They found the 6A variant in 2.5 percent of primary colorectal tumors and 1.8 percent of head and neck primary tumors, and in 29.5 percent of the tumors that had metastasized to the liver. The tumors had acquired the variant as a mutation. The variant was not found as a mutation in the breast tumors.

“We believe that the presence of the 6A variant places an individual at greater risk for developing some type of cancer compared with someone without the variant, and that this has important public health implications,” Weghorst says.

Overall, the evidence from the study suggests that the 6A mutation boosts cancer-cell growth and tumor metastasis. This, in turn, suggests that the molecule would make a good target for anticancer drugs that block the action of the 6A molecule.

Funding from the National Cancer Institute, the National Institute of Dental and Craniofacial Research, the Illinois Chapter of the American Cancer Society, the Walter S. Mander Foundation, The V Foundation, the Dutch Cancer Society and the Netherlands Organization for Scientific Research supported this research.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Life Sciences:

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

For a chimpanzee, one good turn deserves another

27.06.2017 | Life Sciences

Collapse of the European ice sheet caused chaos

27.06.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>