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Blood mutations could contaminate genetic analyses of tumours

Genetic mutations in blood cells that have made their way into tumours could be red herrings that mislead physicians looking for genetic changes in tumours that are helping to drive the cancer. This finding is significant because physicians could make misinformed treatment decisions.

University of North Carolina Lineberger Comprehensive Cancer Center researchers and colleagues will report findings at the 2018 American Society of Clinical Oncology Annual Meeting on Monday, June 4, that show that blood cell mutations accounted for as many as 8 percent of the mutations identified in large-scale genetic sequencing efforts at two major academic centres.

“Next-generation sequencing of solid tumours is intended to identify acquired mutations within tumour tissue,” said the study’s first author Catherine C. Coombs, an associate member of UNC Lineberger and an assistant professor in the UNC School of Medicine Division of Hematology/Oncology. “The identification of acquired mutations in blood cells could lead to errors in interpretation of sequencing results.”

For the study, researchers reviewed data from patients with solid tumour cancers who had genetic sequencing tests performed by Foundation Medicine as part of their routine clinical care at the N.C. Cancer Hospital and the Moffitt Cancer Center between 2013 and 2017. They also analysed sequencing results for blood samples. A subset of patients at the N.C. Cancer Hospital had their tumours and their blood sequenced through UNCseq, a genetic sequencing clinical trial run by UNC Lineberger researchers. For patients at Moffitt Cancer Center, they compared Foundation Medicine results to sequencing results from banked blood samples.

The researchers analysed the data to identify mutations more commonly seen in blood cells. They found that “clonal haematopoiesis,” which are acquired mutations in blood cells, accounted for 8 percent of the mutations.

“The presence of clonal haematopoiesis mutations on next-generation sequencing reports from solid tumour biopsies can confound assay interpretation with the risk of misguided application of targeted therapies,” Coombs said.

Researchers say further work must be done to develop standard processes for differentiating mutations that occur in the blood versus the tumour in order to ensure accuracy in the tests for physicians who are using the sequencing results to choose personalized treatments for patients. In addition, the study shows an advantage to “paired” sequencing tests, which evaluate mutations in both the blood and the tumour.


University of North Carolina Lineberger Comprehensive Cancer Center