Thousands of <em>BRCA1</em> Genetic Variants Functionally Characterized
Thousands of <em>BRCA1</em> Genetic Variants Functionally Characterized

Thousands of BRCA1 Genetic Variants Functionally Characterized

The researchers catalogued 3,893 variants of the gene implicated in cancer using CRISPR.

Sep 13, 2018
Sukanya Charuchandra

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Nearly 4,000 genetic variants of BRCA1, a tumor-suppressing gene whose loss of function can lead to breast and ovarian cancer, have been functionally classified, according to a study published September 12 in Nature. These findings could help with ascribing cancer risk to unknown variants. 

“This work was really tour de force,” Susan Domcheck, an oncologist at the University of Pennsylvania who was not involved in the study, tells The Atlantic

According to Nature, millions of people have undergone BRCA sequencing, but the effects of many variants are not well understood by medical practitioners. 

Using CRISPR, the researchers made 3,893 variants of the gene and integrated them into a haploid human cell line programmed to die if nonfunctional BRCA1 were present. This helped them observe which sequences let cells survive and which killed the cells. The results of variants already known to be benign or to result in tumors clinically correlated with their data.

According to STAT, Heidi Rehm of Harvard Medical School considers the results “well validated” and suggests that clinicians “should weigh” the data on these newly characterized variants in their health care advice. 

Others suggest the data may need real-world testing. In a commentary on the study, Stephen Charnock at the National Institutes of Health says, “In vitro data alone should not be used as the basis for medical advice—at least until the approach has been clinically validated.”

“Our hope is that this database will continue to grow and will become a central point for guiding the interpretation of actionable variants as they are first observed in women,” coauthor Lea Starita at the University of Washington School of Medicine, says in a statement