Novel driver gene MDC1 confers homologous recombination repair deficiency and genomic instability in chemoresistant relapsing ovarian cancer

Using both next generation and ultra long read sequencing to analyze single nucleotide and structural variants (SVs) we discovered that although tumors from the same patient remained relatively stable, homologous recombination repair proficient (HRP) and homologous recombination repair deficient (HRD) tumors presented with distinct clonal profiles.

SV signature analysis revealed three distinct classes: tumors defined by DNA losses, DNA gains, and copy number neutral changes. Each class displayed structural variation affecting distinct regions of the genome. Ultra long read sequencing validated most of the SVs identified in short read sequencing and identified additional SVs.