Gene editing reveals the effect of thousands of variants in a key cancer gene

Chanock, Stephen J.

doi:10.1038/d41586-018-06022-y

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12 September 2018

Gene editing reveals the effect of thousands of variants in a key cancer gene

Gene editing has now been used to introduce every possible single-nucleotide mutation into key protein-coding regions in the cancer-predisposition gene BRCA1, to identify the variants that are linked to cancer risk.

Stephen J. Chanock⁰

Stephen J. Chanock
1. Stephen J. Chanock is in the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
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For decades, cancer geneticists have been trying to understand which changes in the sequence of the BRCA1 gene predispose affected individuals to developing breast or ovarian cancer. Extensive efforts have focused on interpreting the plethora of genetic variants in BRCA1, using clinical observations to determine whether this or that variant warrants patient counselling about options for medical intervention¹. Generally, BRCA1 variants are sorted into three categories²^,³: benign variants, which cause no concern; deleterious variants, which can confer a high risk of cancer; and an unsettling intermediate known as variants of uncertain significance (VUS). Hardest to classify are variants that arise only rarely, of which there are thousands for BRCA1. Conventionally, genetic sleuthing has focused on families or populations within which certain mutations occurred at an unusually high frequency, exposing the effects of deleterious variants. But in a paper in Nature, Findlay et al.⁴ report an innovative laboratory-based approach to assessing the effect of thousands of variants across protein-coding regions of BRCA1.

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Nature 562, 201-202 (2018)

doi: https://doi.org/10.1038/d41586-018-06022-y

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