Cell-free DNA (cfDNA) mutations from clonal hematopoiesis: Implications for interpretation of liquid biopsy tests.

11526Background: A large fraction of cfDNA fragments are derived from hematopoietic sources. Somatic alterations in cfDNA can be tumor-derived but also could represent somatic changes associated with clonal hematopoiesis. We performed deep sequencing of both plasma cfDNA and matched white blood cell (WBC) genomic DNA (gDNA) to determine the contribution of clonal hematopoiesis to the variants observed in cfDNA. Four cohorts were investigated: metastatic breast (BC), non-small cell lung (NSCLC), castration-resistant prostate cancer (CRPC), and non-cancer participants (pts). Methods: Metastatic cancer pts with de novo or progressive disease were prospectively enrolled. Non-cancer pts were blood bank donors. Plasma cfDNA and matched WBC gDNA were sequenced using a targeted 508-gene panel (2 Mb) to > 60,000X raw depth. Variant calling used a novel pipeline that employed molecular barcoding for error suppression followed by de novo assembly and graph-based variant calling. Results: Of 151 metastatic cancer pts...