Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New method provides fast, accurate, low cost analysis of BRCA gene mutations in breast cancer

06.08.2012
Next generation sequencing approach reported in the Journal of Molecular Diagnostics

Individuals with mutations in BRCA1 and BRCA2 genes have a significantly higher risk of developing breast and ovarian cancers. Families at risk have been seeking genetic testing and counseling based on their mutation carrier status, but the standard method of direct sequencing is labor-intensive, costly, and it only targets a part of the BRCA1 and BRCA2 genes.

A group of Canadian scientists has developed a new sequencing approach to provide a more effective method of BRCA1/2 mutational analysis. Their work is published in the September issue of The Journal of Molecular Diagnostics.

"A comprehensive understanding of BRCA1/2 genotypes and the associated tumor phenotypes is needed to establish targeted therapies," notes lead investigator Hilmi Ozcelik, PhD, of the Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. "Recent studies have suggested that certain chemical inhibitors are effective for the treatment of breast cancer in patients with BRCA1/2 mutations. Therefore, availability of new, affordable, and comprehensive technologies to screen for these mutations will be critical to identify patient-candidates for targeted therapies."

The investigators used a technique called long range PCR to generate amplified BRCA1/2 fragments, known as amplicons, from the DNA of 12 familial breast cancer patients. The amplicons were screened using deep sequencing, also known as Next Generation Sequencing (NGS), which allows for the simultaneous screening of millions of DNA molecules, thereby dramatically increasing speed and throughput. While conventional screening methods target only the exons of BRCA1/2, deep sequencing can screen the entire genomic region, including introns and untranslated regions. The specimens had been previously analyzed using conventional methods, allowing for a comparison of results.

In addition to identifying one genetic variant that was missed due to human error, the new method successfully identified all of the expected BRCA1/2 variants. They identified both exonic and exon/intron boundary variants. The test was done at a very low cost, and with a turnaround time of 12 days. "One of the key advantages of workflow of long-range PCR is the ability to visually detect large genomic duplications, deletions, and insertions," notes Dr. Ozcelik. "When combined with next generation sequencing, long range PCR can be a powerful tool in the detection of BRCA variants in the clinical setting. Our method confirmed the presence of variants with very high accuracy, and without false-positive results."

Long-range PCR and next generation sequencing identified a wide range of intronic BRCA1/2 variants, both commonly occurring and rare, that individually or in combination may impact BRCA1/2 function. Dr. Ozcelik notes that despite a small sample size, the data shows great variability in the number, type, and frequency of variants that can be identified from familial breast cancer patients.

"Our challenge now is to establish analytical methods that systematically investigate this more comprehensive data in order to provide better risk information for clinical management of the disease," says Dr. Ozcelik. "Given the extensive level of genetic information acquired from each patient, profiles can be constructed in breast cancer patients compared to population controls to produce a more effective means of generating BRCA1/2-associated risk to the individuals and their families.

David Sampson | EurekAlert!
Further information:
http://www.elsevier.com

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 >>>