Lab test can identify dangerous gene mutations, study finds

NEW YORK – Scientists have discovered that they have found a new way to determine whether specific genetic abnormalities are likely to make people sick, in order to avoid frustrating uncertainty surrounding DNA test results.

The researchers used genetic engineering to create thousands of tiny variations in a gene linked to breast cancer and tested each of them in a laboratory to predict whether it would promote the disease if it appeared in a family. no one.

When these predictions were verified against what scientists already knew about the BRCA1 gene, "we were very specific," said Lea Starita of the Brotman Baty Institute for Precision Medicine in Seattle.

The technique, which she and her colleagues hope to expand to other genes, aims to alleviate a frustrating problem in genetic testing. Sometimes these tests reveal an abnormality in a gene linked to the disease, but nobody knows if this quirk is dangerous. This is what is called an "uncertain variant of meaning", or SUV.

Such a result can cause anxiety and worse: experts talk about women who have had the breasts removed after learning that they were infected with a gene linked to breast cancer. Years later, research

The new work aimed to identify tiny variants of the BRCA1 gene's DNA code that prevent it from working. Mutations that deactivate this gene greatly increase the risk of breast and ovarian cancer.

The results were published Wednesday by the journal Nature.

The researchers created nearly 4,000 tiny variations in the key sections of the gene. Then they tested whether each variant paralyzed the gene in cells that die when BRCA1 does not work. This allows them to predict which variations would promote cancer if they were found in a person.

To check the accuracy of their forecasts, they looked at a database listing the effects of BRCA1 variants. The results showed that 169 of the variants that they had generated had been declared dangerous in the database and that the test had predicted in 162 of them. Similarly, the test correctly ranked 20 of the 22 variants considered harmless in the database.

The researchers plan to extend the test to other genes that may predispose people to cancer. It could also be extended to genes related to other diseases.

Going beyond the genes of cancer would raise the difficult challenge of finding appropriate laboratory tests, said Jay Shendure of the Baty Institute. His salary is paid for by the Howard Hughes Medical Institute, which also supports the Associated Press Department of Health and Science.

The approach makes it possible to test the variations even before they are seen in people, so that their meaning can be immediately known once they appear for the first time in a genetic test, did he declare.

The results look promising for SUV resolution in BRCA1 when they are used with other information, said Heidi Rehm of Massachusetts General Hospital in Boston and Broad Institute in Cambridge, Massachusetts. She did not participate in the study.

BRCA1 has a low rate of SUV test results, but Rehm said that she thought that the general approach could also be applied to other genes.

Further research will be needed to confirm the new useful approach for the BRCA1 gene and other genes.

"I really hope" that her promise will be confirmed, said Julie Eggington, CEO of the Center for Genomic Interpretation in Sandy, Utah.