Non-invasive genotyping of metastatic colorectal cancer using circulating cell free DNA

Publication date: Available online 12 June 2019Source: Cancer GeneticsAuthor(s): Xuemei Shi, Dzifa Y. Duose, Meenakshi Mehrotra, Michael A. Harmon, Peter Hu, Ignacio I. Wistuba, Scott Kopetz, Rajyalakshmi LuthraABSTRACTCirculating cell-free DNA (ccfDNA) in plasma provides an easily accessible source of circulating tumor DNA (ctDNA) for detecting actionable genomic alterations that can be used to guide colorectal cancer (CRC) treatment and surveillance. The goal of this study was to test the feasibility of using a traditional amplicon-based next-generation sequencing (NGS) on Ion Torrent platform to detect low-frequency alleles in ctDNA and compare it with a digital NGS assay specifically designed to detect low-frequency variants (as low as 0.1%) to provide evidence for the standard care of CRC. The study cohort consisted of 46 CRC patients for whom matched samples of formalin-fixed, paraffin-embedded tumor tissue, plasma, and peripheral blood mononuclear cells were available. DNA samples from different sources were sequenced on different platforms using commercial protocols. Our results demonstrate that the ccfDNA sequencing with the traditional NGS can be reliably used in an integrated workflow to detect low-frequency somatic variants in CRC. We found a high degree of concordance between traditional NGS and digital NGS in profiling mutant alleles in ccfDNA. These findings suggest that the traditional NGS is a viable alternative to digital sequencing of ccfDNA at allele frequ...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research