Multigene panel test could be useful to detect patients with hereditary kidney cancer syndrome

Sep 13 2017

A multigene panel test could be a useful diagnostic tool to help clinicians identify patients with a hereditary kidney cancer syndrome, according to the results of a study published in Cancer.

"We know that a large number of patients with kidney cancer have an inherited predisposition," study researcher Brian Shuch, MD, of the department of urology at Yale School of Medicine in New Haven, Connecticut, told Cancer Therapy Advisor. "We are now able to test these patients with a multigene panel that can facilitate identification of a germline variant."

According to Dr Shuch, the panel tested for 19 genes currently known to increase the risk for kidney cancer. All of these genes are inherited genes -; called germline variants -; and are possessed in every cell of the patient's body.

The study included 1235 patients who underwent targeted multigene panel testing between 2013 and 2016. The median age of patients was 46, significantly younger than the United States population of people with kidney cancer (46.2 vs 63.2; P < .001).

The panel identified several inherited genes including folliculin (FLCN) and fumarate hydratase (FH). Overall, 6.1% of patients were positive for a germline variant, 75.5% of patients were negative, and 18.4% had inconclusive results. Mutations were found in 15 of the genes evaluated in the test.

Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance and were identified in 2.7%, 2.2%, and 1.7% of patients, respectively.

The researchers noted that early onset age was the only factor identified as predictive of a positive test on multivariate analysis (odds ratio = 0.975; P = .0052).

Real-World Application

Hereditary kidney cancer syndromes are often diagnosed by astute clinicians who recognize that there is more to a patient's diagnosis then just the random event of getting cancer, according to Dr Shuch.

“If the clinician is not very astute, or does not have a good recognition or knowledge of kidney cancer syndromes, they may miss the diagnosis of a condition that predisposes the patient to that cancer, which may put [the patient] at risk to develop other types of cancer and places other family members at risk for kidney cancer or other diseases,” Dr Shuch explained.

Anyone with a significant family history for kidney cancer or who has a clinical manifestation of a specific cancer-causing syndrome should probably be tested if they meet the testing criteria for a specific syndrome, Dr Shuch said.

“This test would be useful for someone who is affected with kidney cancer where the clinician has some increased suspicion that it may not be a sporadic event,” Dr Shuch said.

“In the past the clinician would need to rely on a strong understanding of each cancer syndrome and decide to individually test each gene one at a time in sequential fashions. This is more of a shotgun approach to test all genes at once,” he said. “It is more cost effective and has a higher chance of finding the cause of the cancer.”

Similar to false positives in diagnostic tests, one possible drawback to the multigene panel is the discovery of a gene of unknown significance.

“Sometimes a patient has a variant that is different from normal, but it is unclear if the variant is associated with a disease or the cancer they developed,” Dr Shuch explained. “In testing, it is not always black or white, positive or negative. There are mutations that are disease-causing mutations, there are mutations that may not be significant and are not associated with anything, and then there are completely normal test results.”