Photo: JOHN HART, STATE JOURNAL ARCHIVES
A Promega Corp. test of how well tumor cells correct DNA errors, developed through scientific serendipity from NASA research, can identify cancer patients likely to have Lynch syndrome, an inherited disorder that increases the risk of colon, endometrial, stomach, ovarian, and other cancers.
The test for microsatellite instability, or MSI, can also help doctors decide whether to treat cancer patients with new immunotherapies.
MSI testing measures how well cells repair mistakes made during DNA replication when cells divide. Tumors with significant microsatellite instability, known as MSI-high, have defective repair mechanisms and are likely to be caused by Lynch syndrome gene mutations, said Annette Burkhouse, senior medical science liaison at Promega.
They’re also likely to respond well to immunotherapies, presumably because they produce more “foreign” proteins detected by the immune system.
Fitchburg-based Promega got a grant from NASA more than 20 years ago to study the effect of deep-space radiation on the DNA of astronauts, which led to the release of a research-grade MSI testing kit in 2004. The significance of such testing grew in 2017, when the Food and Drug Administration approved the immunotherapy drug Keytruda for MSI-high tumors. Promega has applied for FDA approval of a clinical-grade test, which could expand its use.
Patients with MSI-high tumors can undergo genetic testing to confirm if they have mutations in one of five genes involved in Lynch. Another type of testing, called immunohistochemistry, or IHC — which Promega is not involved in — can also screen tumors for a patient’s likelihood of having Lynch, also subject to confirmation through genetic testing.
Many hospitals, such as those in the Ohio Colorectal Cancer Prevention Initiative, have started using one or both testing methods to screen all colorectal tumors for the defective repair mechanisms.
In recent years, UW Hospital has started doing IHC testing on all colorectal, endometrial and gastrointestinal tumors, including stomach, pancreas, esophageal, gall bladder and small intestine tumors, said Dr. Jennifer Weiss, director of UW Health’s Gastroenterology Genetics Clinic.
IHC or MSI testing is also done on some other tumors to evaluate the likelihood of Lynch or to determine whether to use immunotherapy drugs, Weiss said.
About 16% of people with colon cancers diagnosed before age 50 have tumors caused by inherited genetic mutations, and BRCA and other genes are involved in some breast, ovarian and other cancers. That had led some researchers to push for genetic testing of patients without the intermediate step of IHC or MSI testing, Weiss said.