Cell-Free-DNA-Based Copy Number Index Score in Epithelial Ovarian Cancer-Impact for Diagnosis and Treatment Monitoring

• Published in: Cancers 2021-12, Vol.14 (1), p.168
• Main Authors: Braicu, Elena Ioana, du Bois, Andreas, Sehouli, Jalid, Beck, Julia, Prader, Sonia, Kulbe, Hagen, Eiben, Bernd, Harter, Philipp, Traut, Alexander, Pietzner, Klaus, Glaubitz, Ralf, Ataseven, Beyhan, Chekerov, Radoslav, Keck, Christoph, Winkler, Thomas, Heikaus, Sebastian, Gellendin, Peggy, Schütz, Ekkehard, Heitz, Florian
• Format: Article
• Language: English
• Subjects: Biopsy; Cancer therapies; Chemoresistance; Chemotherapy; Copy number; Deoxyribonucleic acid; Developmental stages; DNA; DNA sequencing; Genomes; Genomic instability; Gynecology; Medical screening; Mutation; Next-generation sequencing; Ovarian cancer; Patients; Plasma; Platinum; Surgery; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14010168

Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment. Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set. Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively. ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor.