NOV 09, 2020 8:47 AM PST

Potential Problems with Liquid Biopsies

WRITTEN BY: Carmen Leitch

Liquid biopsies are tests that look for biomarkers in the blood, which can help inform the treatment of cancer. The tool is known as a way to characterize tumors without using invasive procedures; it is meant to analyze DNA shed from tumors, migrating in the blood. But when there are genetic mutations that are not related to cancer also floating around in the blood, it can confound the results.

"You can actually measure what's happening with a patient's tumor by taking a blood draw," said Dr. Colin Pritchard, associate professor of laboratory medicine and pathology at the University of Washington School of Medicine in Seattle.

There are two recently approved cancer treatments that might be recommended when certain mutations are identified in cell-free DNA mutations in the plasma of prostate cancer patients. However, blood cells can release DNA that contains other types of genetic mutations that end up in the plasma.

In hematopoiesis, stem cells in the bone marrow generate blood cells. But hematopoietic stem cells can start generating blood cells that are mutated in the same way, which is called clonal hematopoiesis.  Pritchard explained that clonal hematopoiesis can interfere with liquid biopsies. For example, mutations in the genes BRCA1, BRCA2, and ATM have been closely linked to cancer development. But "unfortunately, these same genes are also commonly mutated as a result of clonal hematopoiesis," Pritchard said.

In this study, Pritchard's team investigated whether clonal hematopoiesis is disrupting the results of prostate cancer liquid biopsies.

Reporting in JAMA Oncology, the scientists found that about half of the mutations that liquid biopsies are detecting are not due to tumors; they are due to CHIP (clonal hematopoiesis of indeterminant potential). As the ages of patients increased, these CHIP variants were exponentially more frequent.

A set of images show the UW-OncoPlex cell-free DNA, or "liquid biopsy" work flow at the Genetics and Solid Tumors laboratory at University of Washington Medical Center in Seattle. The special cell-free DNA blood collection tubes on the left have been spun down. The top yellow portion is the plasma. / Credit: Colin Pritchard/UW Medicine

Certain liquid biopsy results may lead clinicians to recommend either the drug rucaparib or olaparib. But an inaccurate result may cause patients to receive unnecessary, unhelpful therapy.

Misdiagnosis could be interfering with the treatment of as many as half of the prostate cancer patients getting liquid biopsies. However, the problem can be solved easily, said the researchers. If the results from the plasma biopsy are compared to genetic results from whole blood, clinicians can differentiate between whether the mutations are coming from tumors or not.

"The good news is that, by looking at the blood cellular compartment, you can tell with pretty good certainty whether something is cancer or something is hematopoiesis," Pritchard said.

There are some caveats to this study, acknowledged the researchers, including a small sample group of only 69 men and similarities in their treatments.

Sources: AAAS/Eurekalert! via University of Washington Health Sciences/UW Medicine, JAMA Oncology

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