Highly sensitive mutation detection methods enable the application of circulating cell-free DNA for molecular tumor profiling. Recent studies revealed that sequencing artifacts, germline variants, and clonal hematopoiesis confound the interpretation of sequencing results and complicate subsequent treatment decision making and disease monitoring. Parallel sequencing of matched white blood cells promises to overcome these issues and enables appropriate variant calling. Comment on: https://doi.org/10.1002/1878-0261.12617.
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