Tracking clonal evolution of drug resistance in ovarian cancer patients by exploiting structural variants in cfDNA.

ABSTRACT: Drug resistance is the major cause of therapeutic failure in high-grade serous ovarian cancer (HGSOC). Yet, the mechanisms by which tumors evolve to drug resistant states remains largely unknown. To address this, we aimed to exploit clone-specific genomic structural variations by combining scaled single-cell whole genome sequencing with longitudinally collected cell-free DNA (cfDNA), enabling clonal tracking before, during and after treatment. We developed a cfDNA hybrid capture, deep sequencing approach based on leveraging clone-specific structural variants as endogenous barcodes, with orders of magnitude lower error rates than single nucleotide variants in ctDNA (circulating tumor DNA) detection, demonstrated on 19 patients at baseline. We then applied this to monitor and model clonal ev

SUBMITTER: Williams MJ 

PROVIDER: S-EPMC11370573 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature