Hybrid Capture-based Genomic Profiling of Circulating Tumor DNA From Patients With Advanced Ovarian Cancer

Objective: We conducted this study to characterize somatic genomic alterations in circulating tumor DNA (ctDNA) from patients with ovarian cancer and compare GAs detected in ctDNA with tissue databases. Methods: Hybrid capture-next generation sequencing genomic profiling of 150 genes was performed on ctDNA from 138 patients with ovarian cancer with 1,500× sequencing depth. The GAs detected in ctDNA were compared with those in our ovarian cancer tissue database (N = 488) and the Cancer Genome Atlas (TCGA) database (N = 489). Results: 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were TP53 (72%), KRAS (11%), LRP1B (10%), ZNF703 (9%) and NF1 (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although PIK3CA and KRAS mutations were more frequent in tissue and ctDNA, respectively (p < 0.05). Gene amplification and rearrangement were more frequent in ctDNA samples. The mutation frequency of homologous recombination repair associated-genes, VEGF signal/angiogenesis pathways, RAS pathways, NOTCH pathways and MSI-H ratio was not statistically different either in ctDNA or in tissue database. However, the mutation frequency of AKT, PIK3CA, PTEN and STK11 in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (p < 0.05). Conclusions: Our results suggest that genomic profiling of ctDNA could detect somatic GAs in a significant subset of patients with ovarian cancer. Hybrid capture-NGS based on liquid biopsy has the potential capability to serve as a substitute to tissue biopsy and further studies are warranted.