AUTHOR=Shen Wenbin , Shan Boer , Liang Shanhui , Zhang Junling , Yu Yangyang , Zhang Yuzi , Wang Guoqiang , Bai Yuezong , Qian Bing , Lu Jin , Jiang Zhi 

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

JOURNAL=Pathology and Oncology Research

VOLUME=27

YEAR=2021

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.581534

DOI=10.3389/pore.2021.581534

ISSN=1532-2807

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> 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 <italic>Cancer</italic> Genome Atlas (TCGA) database (N = 489).</p><p><bold>Results:</bold> 115 patients (83%) had at least 1 GA detected in ctDNA. The most frequently altered genes detected in ctDNA were <italic>TP53</italic> (72%), <italic>KRAS</italic> (11%), <italic>LRP1B</italic> (10%), <italic>ZNF703</italic> (9%) and <italic>NF1</italic> (8%). Comparative analysis with our tissue database showed similar frequencies of GAs per gene, although <italic>PIK3CA</italic> and <italic>KRAS</italic> mutations were more frequent in tissue and ctDNA, respectively (<italic>p</italic> &lt; 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 <italic>AKT</italic>, <italic>PIK3CA</italic>, <italic>PTEN</italic> and <italic>STK11</italic> in PI3K/AKT/mTOR pathway was significantly lower than that in tissue samples (<italic>p</italic> &lt; 0.05).</p><p><bold>Conclusions:</bold> 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.</p>