Quantity of KRAS mutations in cell-free DNA is associated with survival of patients with advanced cancers

摘要: Background: Cell-free (cf) DNA from plasma offers an easily obtainable material for KRAS mutation analysis for diagnostics and monitoring. There is emerging evidence that the percentage of mutant cfDNA in the wild-type background (mutant allele fraction, MAF) and/or absolute quantity of mutant cfDNA can be associated with survival of patients with advanced cancers.Methods: Plasma-derived cfDNA from patients with progressing advanced cancers was purified and 16 ng of DNA was tested with a KRAS multiplex assay to distinguish the wild-type allele from 7 of the most common mutations in the G12 and G13 hotspot of exon 2 using the QX200 Droplet Digital PCR™ platform (Bio-Rad). Results were compared to mutation analysis of archival primary or metastatic tumor tissue obtained at different points of clinical care from a CLIA-certified laboratory and clinical outcomes including survival.Results: Of the 117 …