The recognition of a causal link between mutations in BRCA1 and BRCA2 genes and increased risk of developing breast and ovarian cancer has intensified the demand for genetic testing. Identifying mutations in these large genes by conventional methods can be time consuming and costly.
A report in the November issue of the Journal of Molecular Diagnostics describes a new technique using second-generation sequencing technology that is as sensitive as the standard methodology but has the potential to improve the efficiency and productivity of genetic testing laboratories.
"In our laboratory, approximately 25% of high risk patients who undergo BRCA1 or BRCA2 testing will generate a result with a real or ambiguous relationship to hereditary cancer risk, and so testing for these mutations is an important tool to identify individuals who would benefit from preventative surgery or increased breast cancer surveillance," says lead investigator Aly Karsan, MD, of the Genome Sciences Centre and Department of Pathology of the BC Cancer Agency.
Dr. Karsan, who says his institution currently receives over 500 requests annually for such genetic testing, expects demand to rise and wait times to increase as public awareness broadens, especially following such high-profile patients as Angelina Jolie. Fueling the demand will be identification of additional suspect genes and discovery of genetic factors predictive of response to new therapies. As a result, there is a need for faster and low-cost testing with additional analytic capabilities.
Increased efficiency of the methodology developed offers additional benefits to patients. The investigators envision that more women will be able to be tested, including those without family history of breast or ovarian cancer. Another potential advantage will be that more genomic regions can be analyzed by a single test, allowing simultaneous analysis of other genes that also may be contributing to breast or ovarian cancer susceptibility.
The investigators warn that as more women undergo genetic testing, there is increased likelihood of finding variants of unknown significance or incidental discoveries. They caution that interpretation of these variants can be difficult and time consuming, and procedures should be developed for reporting these results to physicians and patients.
The second-generation sequencing assay described in the current report uses automated small amplicon PCR followed by sample pooling and sequencing with a second-generation instrument. The target region selected was thought to encompass the majority of pathogenic sequence changes in BRCA1 and BRCA2.
The investigators tested the assay using a set of 91 patient genomic DNA samples, 48 selected retrospectively and 43 prospectively. Comparing their results to those obtained by the standard dideoxy sequencing methodology, the researchers found 100% concordance between the two methods, with no false-positive or false-negative predictions. The method generated high-quality sequence coverage across all targeted regions with median coverage greater than 4,000-fold for each pooled sample. After some technical adjustments (such as setting the maximum depth parameter to an arbitrarily high value of 500,000 using SAMtools software and selecting 100,000 as the on-target alignments threshold), the method proved sensitive and specific for detecting variants in genetic sequences.
Eileen Leahy | EurekAlert!
How gut bacteria can make us ill
18.01.2017 | Helmholtz-Zentrum für Infektionsforschung
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction