Are genetic testing criteria redundant in the light of next generation sequencing technologies?

29 July 2016

A PHG Foundation report published today urges a considered approach to using technologies such as whole genome sequencing (WGS) to test for high risk cancer gene mutations in people with no family history of the disease. A paper based on the PHG Foundation’s work was published in Hereditary Cancer in Clinical Practice earlier this year.   

Technologies such as WGS greatly enhance the speed and ease of testing for cancer-associated mutations. Some organisations such as the American College for Medical Genetics & Genomics (ACMG) and Genomics England in its 100,000 Genomes Project protocol recommend routine screening for mutations in medically actionable genes whenever WGS is done regardless of indication. These include the BRCA1 and BRCA2 genes associated with hereditary breast and ovarian cancer. The report takes the example of testing for breast cancer mutations, but its findings are applicable across a range of inherited conditions. 

Testing for germline mutations in breast cancer-associated genes is traditionally reserved for patients whose age, family and personal cancer histories place them above a testing threshold. The prospect of testing individuals who would not meet usual testing criteria for these mutations using WGS raises uncertainties around the level of cancer risk and the clinical utility of the results to inform clinical care. These uncertainties must be acknowledged and, as far as possible, addressed if widespread testing is to become routine, say the report authors, who urge the robust evaluation of developing practice and research in this area.

In producing the report, Whole genome sequencing for breast cancer risk testing,  the authors examined population penetrance and gene-disease association for inherited breast cancer gene variants, outlined factors to be considered in order to establish test performance for WGS-based testing for BR CA1 and BRCA2 mutations and  described the implications for patients, clinicians and health services.  

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