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    Skin Cancer

    New blood tests can detect melanoma in patients without BRAF or NRAS mutations

    April 2, 2017

    |

    by Emily Innes-Leroux, Associate Editor

    Genetic testing of tumour and blood fluid samples from people with and without one melanoma has shown that two new blood tests can reliably detect previously unidentifiable forms of the disease, according to a poster presentation.

     

    Researchers at NYU Langone Medical Center and its Perlmutter Cancer Center, who led the study, said having quick and accurate monitoring tools for all types of metastatic melanoma may make it easier for physicians to detect early signs of cancer recurrence.

     

    This poster presentation is on display at the annual meeting of the American Association of Cancer Research (AACR) in Washington, D.C. from Apr. 1 to Apr. 5, 2017. Abstract #743, and poster board #9, is titled “Detection of TERT C228T and C250T promoter mutations in melanoma tumor and plasma samples using novel mutation-specific droplet digital PCR assays.”

     

    The new blood tests, which can be evaluated in 48 hours, were developed in conjunction with Bio-Rad Laboratories in Hercules, Calif. At this time, the tests are only available for research purposes.

    According to the study authors, the new tools are the first to identify melanoma DNA in the blood of patients whose cancer is spreading and who lack defects in either the BRAF or NRAS genes. Together, BRAF and NRAS mutations account for over half of the 50,000 cases of melanoma diagnosed each year in the U.S., and each can be found using existing tests. However, the research team estimates that the new tests, once they become available for use in clinics, will be able to detect the majority of all melanomas.

     

    “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 study investigator and dermatologist Dr. David Polsky, in a press release.

     

    Dr. Polsky, the Alfred W. Kopf, MD, Professor of Dermatologic Oncology at NYU Langone and director of its pigmented lesion section in the Ronald O. Perelman Department of Dermatology, will present his team’s latest findings at the annual meeting of the AACR on Apr. 2.

     

    The new tests, said Dr. Polsky, monitor circulating tumour DNA (ctDNA), which are released into the blood when tumour cells die and break apart. Specifically, the test detects evidence of changes in the chemical building blocks (or mutations) of a gene that controls telomerase reverse transcriptase (TERT), a protein that helps cancer cells maintain the physical structure of their chromosomes.

     

     

    Dr. Polsky said the detected changes occur in mutant building blocks, in which a cytidine molecule in the on-off switch for the TERT gene is replaced by another building block, thymidine. Either mutation, C228T or C250T, results in the switch being stuck in the “on” position, letting tumour cells to multiply.

     

     According to Dr. Polsky, the blood tests may have advantages over current methods for monitoring the disease because the tests avoid the radiation exposure that comes with CT scans, and the tests can be performed more easily and more frequently.

     

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

     

    As part of the ongoing study, researchers checked results from the new tests against 10 tumour samples taken from NYU Langone patients diagnosed with and without metastatic melanoma. They also tested four blood plasma samples from NYU Langone 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, they said, for samples with as little as 1% of mutated ctDNA in a typical blood plasma sample of 5 mL. Meanwhile, TERT mutations were absent in tests of normal blood plasma and tonsil tissue.

     

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

     

     Funding support for the study was provided by National Cancer Institute grant R21 CA198495, with in-kind support from Bio-Rad, which provided chemical supplies.

     

    More information regarding Dr. Polsky’s previous research can be found on DERM.city.

    Tags:

    Melanoma

    BRAF

    Blood test

    American Association of Cancer Research

    Dermatology

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