Innovative Gene Testing Technology Finds Cancer Risks

A new method has been developed for identifying mutations and prioritizing variants in breast and ovarian cancer genes, which will not only reduce the number of possible variants for doctors to investigate, but also increase the number of patients that are properly diagnosed.

Advances in next generation sequencing (NGS) have enabled panels of genes, whole exomes, and even whole genomes to be sequenced for multiple individuals in parallel. These platforms have become so cost-effective and accurate that they are beginning to be adopted in clinical settings, as evidenced by recent government approvals.


Genomic scientists at Western University (London, ON, Canada) applied their newly developed methodology to 102 individuals at risk or with a diagnosis of inherited breast cancer. The team also studied 287 women with no known mutations in a separate study. They captured and enriched for coding and non-coding variants in genes known to harbor mutations that increase hereditary breast and ovarian cancer (HBOC) risk.

They increased sequence coverage in complete genes with capture probes by enriching for both single-copy and divergent repeat (more than 30 % divergence) regions, such that, under the correct hybridization and wash conditions, all probes hybridize only to their correct genomic locations. This step was incorporated into a modified version of in-solution hybridization enrichment protocol, in which the majority of library preparation, pull-down, and wash steps were automated using a BioMek FXP automation workstation (Beckman Coulter, Mississauga, Canada).

The scientists identified 15,311 unique variants, of which 245 occurred in coding regions. With the unified information theory (IT)-framework, 132 variants were identified and 87 functionally significant variants of uncertain significance (VUS) were further prioritized. An intragenic 32.1 kb interval in Breast Cancer 2 genes (BRCA2) that was likely hemizygous was detected in one patient. They also identified four stop-gain variants and three reading-frame altering exonic insertions/deletions (indels). After completing the analysis, between zero and three variants were prioritized in most patients.

Peter K. Rogan, PhD, the senior author of the study, said, “When a woman with a family history of breast cancer sees her physician, they want to know if they have a mutation in breast/ovarian cancer genes. All of the patients that we studied had been sequenced for BRCA1 or BRCA2. The causative cancer gene variants are hiding in plain sight in these and other cancer genes, but the original testing laboratory did not recognize them. Our approach can reveal gene variants that might explain their increased risk for cancer.” The study was published on April 11, 2016, in the journal BMC Medical Genomics.

Related Links:
Western University
Beckman Coulter