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New Gene-Based Blood Tests Identify Skin Cancers

Experimental assays show promise in monitoring patients with melanoma

Genetic testing of tumor and blood fluid samples from people with and without one of the most aggressive forms of skin cancer has shown that two new blood tests can reliably detect previously unidentifiable forms of the disease, according to a report from New York University’s Langone Medical Center and its Perlmutter Cancer Center.

The new tests, which take only 48 hours, were developed in conjunction with Bio-Rad Laboratories in Hercules, California. Currently, the tests are available only for research purposes.

The new assays are the first to identify melanoma DNA in the blood of patients whose cancer is spreading and who lack defects in either BRAF or NRAS genes (known to drive cancer growth), according to the researchers. Together, BRAF and NRAS mutations account for more than half of the 50,000 cases of melanoma diagnosed each year in the United States. Both BRAF and NRAS mutations can be found by existing tests, but the researchers estimate that when their new tests become available for use in clinics, the majority of all melanomas will be detectable.

“Our goal is to use these tests to make more-informed treatment decisions and, specifically, to identify as early as possible when a treatment has stopped working, cancer growth has resumed, and the patient needs to switch therapy,” said senior investigator David Polsky, MD, PhD.

The new tests monitor blood levels of DNA fragments––known as circulating tumor DNA (ctDNA)––that are released into the blood when tumor cells die and break apart, Polsky explained. Specifically, the tests detect evidence of mutations in the chemical “building blocks” of a gene that control telomerase reverse transcriptase (TERT), a protein that helps cancer cells maintain the physical structure of their chromosomes.

Polsky said that the detected changes occur when a cytidine molecule in the “on/off” switch for the TERT gene is replaced by a thymidine molecule. Either mutation, C228T or C250T, results in the switch being stuck in the “on” position, helping tumor cells to multiply.

According to Polsky, the new tests may have advantages over current methods for monitoring melanoma because they avoid the radiation exposure that comes with computed tomography (CT) scans, and the tests can be performed more easily and more often.

The Bio-Rad tests, once clinically validated, are likely to gain widespread use, he said, because his previous research has shown that similar blood tests for BRAF and NRAS mutations worked better in identifying new tumor growth than did existing blood tests for the lactate dehydrogenase protein. Lactate dehydrogenase levels may spike during aggressive tumor growth, but they may also rise as a result of other diseases and biologic functions.

As part of the ongoing study, the researchers checked results from the new tests against 10 tumor samples taken from patients at the Langone Medical Center who had been diagnosed with and without metastatic melanoma. The investigators also tested four blood- plasma samples from patients with and without the disease. Blood-test results matched correctly in all cases known to be either positive or negative for metastatic melanoma. Successful detection occurred for samples with as little as 1% of mutated ctDNA in a typical blood plasma sample of 5 mL, according to the researchers. TERT mutations were absent in tests of normal blood plasma and tonsil tissue.

Polsky said that further study of the new blood tests is planned to gauge their use in monitoring disease progression in patients with melanoma, and to more-quickly determine when switching to an alternative therapy is warranted, as well as whether the tests can be used to detect other types of cancer, such as brain tumors, that also have TERT mutations.

Source: PR Newswire; April 2, 2017.

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