The dynamic range of circulating tumor DNA in metastatic breast cancer.

摘要: Introduction: The management of metastatic breast cancer needs improvement. As clinical evaluation is not very accurate in determining the progression disease, analysis circulating tumor DNA (ctDNA) has evolved to a promising noninvasive marker disease evolution. Indeed, ctDNA was reported represent highly sensitive biomarker directly reflecting burden and dynamics. However, at present little known about dynamic range patients with cancer. Methods: In this study, 74 plasma samples from 58 metastasized were analyzed microfluidic device determine size distribution copy number changes identified by whole-genome sequencing (plasma-Seq). Furthermore, an index patient we conducted whole-genome, exome, or targeted deep primary tumor, metastases, cells (CTCs). Deep done accurately allele fraction (AFs) mutated fragments. Results: Although all had analyses demonstrated variable AFs mutant We more than 100,000 CTCs detail. first four different regions three lymph node regions, which enabled us establish phylogenetic relationships these lesions, consistent genetically homogeneous Subsequent 551 confirmed serial blood analyses. only 2% 3% each analysis, neither nor dynamics progressive disease. These results together high-resolution fragment sizing suggested that differences phagocytosis degradation mechanisms likely explain occurrence fragments Conclusions: varies substantially This important implications for use as predictive prognostic biomarker.