A new method of detecting the genetic mutation KIT D816V in peripheral blood was able to identify the mutation at a rate comparable to bone marrow testing, according to a study recently published in The Journal of Allergy and Clinical Immunology. KIT D816V is the most common mutation associated with systemic mastocytosis (SM); detection of the mutation can help diagnose the disease.
Scientists widely agree that bone marrow analysis is one of the most effective ways of detecting the genetic mutation KIT D816V. However, false negatives can still occur, especially among patients with indolent SM. This is because patients with indolent SM have periods of low mutation burden, complicating detection. In addition, the sample obtained is sometimes too small for analysis to be accurately performed, and the bone marrow biopsy needed for the test is often uncomfortable for patients.
Droplet digital polymerase chain reaction (ddPCR) is another method that can detect the mutation. This test uses a blood sample instead of bone marrow, but is considered less accurate.
Researchers thus developed the super rolling-circle amplification (superRCA) method, which they claim has at least a 30-fold higher sensitivity for KIT D816V compared with the ddPCR method and can be used with either blood or bone marrow samples.
Researchers looked into peripheral blood KIT D816V detectability by investigating cases assessed centrally by ddPCR. Patients who did not have the mutation in ddPCR tests were assessed using the superRCA. These were then compared with patients who were genetically assessed using bone marrow aspirate. Researchers then compared performance by looking at the Total Symptom Score from the ISM-Symptom Assessment Form, as well as objective measures of mast cell burden between cases detectable via ddPCR and those detectable via superRCA but not ddPCR.
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A total of 371 patients were included in this analysis. Researchers found that 79.5% of cases had mutations identifiable via ddPCR. By combining both ddPCR and superRCA methods, the rate of KIT D816V mutation detection was 94.9%. Local bone marrow KIT D816V testing found that 97% of patients had the mutation. These results showed that while ddPCR testing alone missed many instances of the mutation, ddPCR and superRCA together found almost as many cases as bone marrow testing.
In addition, baseline median serum tryptase levels (a biomarker that is often raised in SM) were significantly higher among patients with mutations identifiable via ddPCR compared with those who had mutation that were missed by ddPCR but found with superRCA.
“The superRCA assay increased [peripheral blood] KIT D816V detection comparable with local BM testing, highlighting the potential for ultra-sensitive testing to improve ISM diagnosis, especially with low baseline serum tryptase,” the research team concluded.
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