Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma

• DOI: 10.1016/j.biopha.2023.115630
• Publication Date: 2023-10-06T02:54:46Z
• Authors: Mai T.N. Nguyen; Anna Rajavuori; Kaisa Huhtinen; Sakari Hietanen; Johanna Hynninen; Jaana Oikkonen; Sampsa Hautaniemi
• Keywords: Concordance; Copy number analysis; Circulating tumor DNA; Amplicon

Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for detecting and profiling longitudinal genomics changes in cancer. While copy-number alterations (CNAs) play major role cancers, treatment effect monitoring using profiles received limited attention compared to mutations. A reason this is the insensitivity of CNA real-life tumor-fraction ctDNA samples. We performed on 152 plasma samples obtained from 29 patients with high-grade serous ovarian cancer (HGSC) sequencing panel targeting over 500 genes. Twenty-one had temporally matched tissue sample pairs, which enabled assessing concordance tissues sequenced same or whole-genome evaluate sensitivity. Our approach could detect concordant most low 5% content highly amplified regions ∼1% content. Longitudinal showed seven out 11 high tumor-content at relapse. These included focal acquired lost copy-numbers, even though genome remained stable. Two displayed profile during therapy. revealed ctDNA-detectable subclonal selection resulting both surgical operations chemotherapy. Overall, data diminished CNAs relapse when pre-treatment results highlight importance genomic well underline usability ctDNA.