False positive plasma genotyping due to clonal hematopoiesis

摘要: Purpose: Plasma cell-free DNA (cfDNA) genotyping is increasingly used in cancer care, but assay accuracy has been debated. Because most cfDNA derived from peripheral blood cells (PBC), we hypothesized that nonmalignant mutations harbored by hematopoietic (clonal hematopoiesis, CH) could be a cause of false-positive plasma genotyping.Experimental Design: We identified patients with advanced non-small cell lung (NSCLC) KRAS, JAK2, or TP53 cfDNA. With consent, PBC was tested using droplet digital PCR (ddPCR) next-generation sequencing (NGS) to test for CH-derived mutations.Results: first studied ddPCR results 58 EGFR-mutant NSCLC. Two had KRAS G12X detected cfDNA, and both were present PBC, including one where the mutation serially 20 months. then 143 NGS 122 NSCLC 5 JAK2 V617F PBC. In addition, 108 cfDNA; 33 mutations, tumor available comparison, absent tumor, consistent CH.Conclusions: find some rare are CH not tumor. Clinicians ordering must prepared possibility plasma, particularly genes mutated CH, may represent true genotype. Efforts use detection need paired so misdiagnosed as occult malignancy. Clin Cancer Res; 24(18); 4437-43. ©2018 AACRSee related commentary Bauml Levy, p. 4352.