This paper details a study that tracked clonal evolution and drug resistance in high-grade serous ovarian cancer (HGSOC) patients. Researchers developed a method called CloneSeq-SV, which combines single-cell whole-genome sequencing (scWGS) with targeted deep sequencing of structural variants (SVs) in cell-free DNA (cfDNA) to monitor co-existing tumor populations over time. The study of 18 patients revealed that drug resistance often arises from the selective expansion of pre-existing clones present at diagnosis, which frequently exhibit distinctive genomic features like oncogene amplifications. Furthermore, SVs proved to be highly specific markers for tracking tumor DNA in cfDNA, offering an advantageous signal-to-noise ratio compared to single nucleotide variants (SNVs), and demonstrating the potential of this approach to inform future evolution-informed adaptive treatment regimens.
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