NCI’s New BRCA1 Test: Broader Utility and Another Challenge to Traditional Genetic Tests
Contributed by Allison Williams Dobson of the Center for Genomics and Society at the University of North Carolina at Chapel Hill.
As reported last week by GenomeWeb, on September 21, 2009, a team led by Shyam Sharan from the National Cancer Institute (NCI) published the development of a new BRCA1 test based on mouse embryonic stem cells. Potentially, the test could prove useful for a much broader range of patients than the controversial Myriad Genetics BRCA1 tests.
The NCI approach focuses more on protein production than DNA analysis. The BRCA1 gene serves as the blueprint for an important tumor suppressor protein. If BRCA1 protein is not produced in sufficient quality and/or quantity, a propensity to develop cancer in the breast tissue often results. The traditional genetic testing approach asks whether a subject carries any of the BRCA1 gene variants that have been associated with increased risk for breast cancer in studies of afflicted families. NCI’s approach asks a significantly different question—rather than focusing on an identified set of “bad” gene variants, NCI asks whether a subject carries BRCA1 variants that serve as adequate blueprints for a functional protein, whether those variants have been previously identified or not. It does this by testing the protein product of the gene.
Until now, women with a family history of breast cancer have been most likely to seek a BRCA genetic test and represent the principal source of BRCA genetic data. Thus Myriad’s patented tests are based on a set of culprit BRCA gene variants found by studying primarily families with a strong propensity toward breast cancer, despite the fact that only 5-7 % of breast cancers are familial. As a result, the Myriad tests only offer useful information about a subset of BRCA1 variants. But many people (both with and without family history) carry other BRCA1 variants of unknown significance (VUS). There just are not enough empirical data yet to support conclusions about the risk associated with VUS.
