Technology as sensitive as standard methodology but more efficient, say researchers in
The Journal of Molecular Diagnostics
“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
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
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.
Technical details of the study
Next-generation sequencing (NGS) refers to technologies that share the ability to parallel sequence millions of DNA templates. The terms second-generation (and third-generation) sequencing are used to describe the evolution of sequencing technology from the first-generation, dideoxy ‘Sanger’ sequencing. The new DNA sequencing technologies are expected to have a significant impact on the detection, management, and treatment of genetic diseases such as ovarian and breast cancer.
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.