![]() ![]() The transformative findings that somatic DNA mutations are present within plasma cell-free DNA (cfDNA) led to the notion of ‘liquid biopsy’, an attractive and less-invasive alternative to solid tumor biopsy for the discovery and longitudinal monitoring of somatic mutations 5, 6, 7, 8, 9. However, there are limited studies of genomic changes in lethal metastatic disease, mainly due to challenges in obtaining biopsies on advanced cancers. The recent revolution in massively parallel DNA sequencing is unravelling the genomic basis of primary cancer 1 and providing important examples of genomic evolution and the hierarchal order of cancer mutations 2, convergent evolution 3, and the development of drug resistance 4. Further refinement may enable simpler and less-invasive methods for longitudinal or theranostic surveillance of metastatic cancer. These pilot findings provide physiological evidence that circulating tumor DNA is accessible by fingerstick and sustains presence/absence of mutation detection after whole-genome amplification. Patient mutations were detected with 100% concordance after WG-RCA, although in some samples, allele frequencies showed greater variation likely due to differential amplification or primer inaccessibility. We identified somatic mutations by targeted sequencing and compared the concordance of mutation detection from venous and amplified capillary samples by droplet-digital PCR. Patient cfDNA was then analyzed with or without a new method for whole genome amplification via rolling-circle amplification (WG-RCA). Fingerstick blood was separated at point-of-care using a novel paper-based concept to isolate plasma centrifuge-free. Matched venous and fingerstick blood were obtained from seven patients with metastatic breast cancer. Here, we test proof-of-concept for using smaller volumes via fingerstick collection. However, obtaining sufficient quantities of cfDNA remains a challenge for assay development and clinical translation consequently, large volumes of venous blood are typically required. The ability to measure mutations in plasma cell-free DNA (cfDNA) has the potential to revolutionize cancer surveillance and treatment by enabling longitudinal monitoring not possible with solid tumor biopsies. ![]()
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