'The premise of precision medicine that we've been promising for 10 or 15 years now is that we'll sequence the genomes of ordinary citizens, and that information will improve their health outcomes. We hope this new study brings us one step closer to delivering on that promise,' said Dr Jay Shendure at the University of Washington in Seattle, senior author of the study.
In the article published in Nature, almost 4000 variants of the early onset BRCA1 gene were studied for their potential contribution towards breast cancer. BRCA1 is a tumour suppressor gene. Mutations that lead to the gene being non-functional can increase the likelihood of a woman developing breast cancer at some point during her life up to 72 percent.
It has recently been stated that screening all women over the age of 30 for their BRCA variation could prevent thousands of cancer cases per year (BioNews 934). Nevertheless, for a large number of BRCA1 mutations, it is not known yet whether they are benign or pathogenic.
To fill in these gaps, the scientists used a human cell line that dies if the BRCA1 gene is not functional and added different single nucleotide mutations of the gene into the cells using CRISPR. They then waited to see if the cells would be viable or not.
By comparing their results for already known variants, they found that cell death is a very good indicator for a benign or carcinogenic mutation, matching the clinical data 96 percent of the time. The researchers hope that their in vitro data might give clinicians some guidance on what to tell patients whose BRCA1 variation has not been looked at yet in humans.
However, this study does not cover all BRCA1 mutations, about 1300 of the 5600 nucleotides were analysed. 'This is an initial stab at this,' Dr Shendure told The Atlantic. 'With further scaling, you can imagine much more ambitious efforts to engineer tens of thousands or hundreds of thousands of mutations into the genome.'
The researchers also plan to use the same approach to investigate lesser studied cancer genes such as BRCA2, PALB2, and BARD16.