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 decipher key principle behind reaction of metalloenzymes
15.01.2018 | Rheinisch-Westfälische Technische Hochschule Aachen

nachricht New method to map miniature brain circuits
15.01.2018 | The Francis Crick 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: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

Im Focus: Autoimmune Reaction Successfully Halted in Early Stage Islet Autoimmunity

Scientists at Helmholtz Zentrum München have discovered a mechanism that amplifies the autoimmune reaction in an early stage of pancreatic islet autoimmunity prior to the progression to clinical type 1 diabetes. If the researchers blocked the corresponding molecules, the immune system was significantly less active. The study was conducted under the auspices of the German Center for Diabetes Research (DZD) and was published in the journal ‘Science Translational Medicine’.

Type 1 diabetes is the most common metabolic disease in childhood and adolescence. In this disease, the body's own immune system attacks and destroys the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fachtagung analytica conference 2018

15.01.2018 | Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

 
Latest News

Black hole spin cranks-up radio volume

15.01.2018 | Physics and Astronomy

A matter of mobility: multidisciplinary paper suggests new strategy for drug discovery

15.01.2018 | Life Sciences

New method to map miniature brain circuits

15.01.2018 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>