Newswise, April 3, 2017 — 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.
Researchers at NYU Langone Medical Center and its Perlmutter
Cancer Center, who led the study, say having quick and accurate monitoring
tools for all types of metastatic melanoma, the medical term for the disease,
may make it easier for physicians to detect early signs of cancer recurrence.
The new blood tests, which take only 48 hours, were developed
in conjunction with Bio-Rad Laboratories in Hercules, Calif. Currently, the
tests are only available for research purposes.
The new tools are the first, say the study authors, to
identify melanoma DNA in the blood of patients whose cancer is spreading and
who lack defects in either the BRAF or NRAS genes, already known to drive
cancer growth.
Together, BRAF and NRAS mutations account for over half of the
50,000 cases of melanoma diagnosed each year in the United States, and each can
be found by existing tests. But the research team estimates that when the new
tests become available for use in clinics, the vast 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,” says senior study investigator and dermatologist David
Polsky, MD, PhD.
Polsky presents his team’s latest findings at the annual
meeting of the American Association for Cancer Research in Washington, D.C.
The new tests, says 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, 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. 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.
Polsky says 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, called thymidine. Either mutation, C228T or
C250T, results in the switch being stuck in the “on” position, helping tumor
cells to multiply.
According to 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 often.
The Bio-Rad tests, once clinically validated, are also likely
to gain widespread use quickly, he says, because his previous research had
shown that similar blood tests for BRAF and NRAS mutations worked better in
identifying new tumor growth than existing blood tests for the protein lactate
dehydrogenase. Lactate dehydrogenase levels may spike during aggressive tumor
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 tumor samples taken from NYU Langone patients
diagnosed with and without metastatic melanoma.
They also tested four blood plasma samples (the liquid portion
of blood) — 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 say, for samples
with as little as 1 percent of mutated ctDNA in a typical blood plasma sample
of 5 milliliters. Meanwhile, TERT mutations were absent in tests of normal
blood plasma and tonsil tissue.
Polsky says further study of the new blood tests are planned
to gauge their use in monitoring progression of the aggressive cancer, and to
more quickly determine when switching to an alternative therapy is warranted,
as well as whether the tests can used to detect other types of cancer, such as
brain tumors, 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.
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