Fergus Couch, Ph.D., chair of Mayo Clinic’s Division of Experimental Pathology and Laboratory Medicine, led a team that recently published new National Institutes of Health and U.S. Food and Drug Administration-approved guidelines for the interpretation of variants in the ataxia telangiectasia mutated (ATM) cancer gene.

Inherited mutations in ATM have been shown to increase the risk of breast and pancreatic cancer and prostate cancer in men. “When recessive, when there are two inherited mutations, it can also cause a disease called ataxia telangiectasia,” Dr. Couch says.

The new guidelines were developed by the ClinGen Hereditary Breast Ovarian and Pancreatic Cancer Variant Curation Expert Panel (HBOP-VCEP), an organization of researchers and variant curators from around the world that Dr. Couch coordinates.

"We have a list of seven cancer genes that we've been trying to develop these new guidelines for," Dr. Couch says. "The pathogenic and benign variants are fairly straightforward, but the trickier ones are variants of uncertain significance. We wanted to help change that."

And so, beginning with the ATM cancer gene, Dr. Couch and other members of the ClinGen HBOP-VCEP spent the last year and a half developing the new interpretation guidelines and putting them through rigorous validation.

"After we developed the new guidelines, we used them to interpret 40 randomly selected variants to ensure they came up with the right results," Dr. Couch says.

Now published by the American Journal of Human Genetics and available for widespread use, Dr. Couch says the guidelines can help clinicians around the world apply the same consistent method of classification to ATM variants.

"Up until now, a lot of companies and countries have been essentially making up their own guidelines because they're not sure how to interpret these variants of uncertain significance," Dr. Couch says. "I think these new guidelines will make it possible for us to now have more of a unified approach across the world for how to do this correctly. And that's what we really want. We want everyone to be on the same page and doing it the same way so that there's consistency for patients."

You can read the full guidelines here. For questions or more information about the guidelines, contact Dr. Couch.

For more information on the hereditary cancer panels offered by Mayo Clinic Laboratories, visit the hereditary cancer testing webpage.