Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

High-powered gene profiles provide clues to genes involved in common form of lung cancer

28.06.2005


Using technology that makes it possible to zoom in on smaller sections of cell chromosomes than ever before, researchers at Dana-Farber Cancer Institute have identified nearly 100 chromosome regions where genes are either over-copied or missing in non-small cell lung cancer. The findings provide new clues about the location of genes potentially involved in the most common type of lung cancer –– and one of the deadliest of all malignancies –– and a range of possible targets for future therapies.



The study will be reported in the Proceedings of the National Academy of Sciences’ Online Early Edition the week of June 27.

"Previous studies have identified a small set of mutated, or abnormal, genes that are associated with non-small cell lung cancer," says the study’s lead author, Giovanni Tonon, MD, PhD, of Dana-Farber. "But we also know that the chromosomes of these cells contain a large number of irregular regions –– where genes have either been deleted or copied over and over again –– which suggests that a large number of cancer genes remain to be discovered. The purpose of this study was to locate the likeliest candidates."


The study is part of a renewed effort by scientists worldwide to uncover the basic biology of lung cancer, the number one cause of cancer-related deaths in the United States. Non-small cell lung cancer (NSCLC) accounts for about 75 percent of all lung cancers and is responsible for nearly 120,000 deaths in this country annually. It is one of the most difficult cancers to treat, with only 15 percent of patients surviving more than five years after diagnosis.

In recent years, technological advances have brought new precision to the search for gene abnormalities associated with cancer. In the current study, Dana-Farber researchers used two forms of microarray technology to bring such abnormalities into focus.

Using tumor samples from 44 NSCLC patients and 34 laboratory-grown lines of NSCLC cells, investigators scanned the cells with high-resolution cDNA (oligonucleotide) microarray equipment to find chromosome regions containing unusual numbers of gene copies. The technology, developed in conjunction with Agilent Technologies, was 50-100 times more powerful than had been used on NSCLC cells in the past, enabling researchers to identify irregular sites more precisely. They found a total of 93 regions, each containing about 11 genes, where gene deletions or over-copying had occurred.

Researchers re-analyzed the tumor and cell samples with the latest oligonucleotide expression microarray technology from Affymetrix, which indicates if individual genes are active. Using this data, they scanned the genes in these 93 regions to see if any were missing (and inactive) or present in unusually large amounts (and therefore highly active) in deleted or overcopied regions, respectively. This enabled them to narrow the search for genes that were the targets of the irregular regions. Intriguingly, all of the genes already known to be involved in NSCLC reside within the abnormal regions identified by the Dana-Farber team.

"This is compelling evidence that we’re on the right track," says the study’s other first author, Kwok-Kin Wong, MD, PhD, of Dana-Farber. "It’s likely that the genetic mutations already linked to NSCLC constitute only a portion of all the genetic errors that drive the disease. Our work provides a good starting point for scientists looking for others."

As part of the study, investigators did microarray analyses on the two major subtypes of NSCLC, adenocarcinoma and squamous cell carcinoma, and found that their genomic profiles overlap in every area but one: squamous cell carcinomas contain an area of gene amplification, or over-copying, not found in adenocarcinomas. Among the few genes in that area is one called p63, which is known to play a role in the ability of skin cells to reproduce. The new finding raises the possibility that adenocarcinoma and squamous cell carcinoma arise from an error in the same cell type and are driven to malignancy by similar genetic routes, the study authors say.

Finally, the researchers compared their data for NSCLC with similar data for pancreatic cancer, and found that both diseases have some chromosomal irregularities in common, suggesting that in both disorders, some of the same genes may be driving the tumors.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu
http://www.pnas.org/papbyrecent.shtml

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

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

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>