A1 Refereed original research article in a scientific journal
Circulating tumor DNA-based copy-number profiles enable monitoring treatment effects during therapy in high-grade serous carcinoma
Authors: Nguyen Mai TN, Rajavuori Anna, Huhtinen Kaisa, Hietanen Sakari, Hynninen Johanna, Oikkonen Jaana, Hautaniemi Sampsa
Publisher: Elsevier Masson
Publication year: 2023
Journal: Biomedicine and Pharmacotherapy
Journal name in source: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Journal acronym: Biomed Pharmacother
Article number: 115630
Volume: 168
ISSN: 0753-3322
eISSN: 1950-6007
DOI: https://doi.org/10.1016/j.biopha.2023.115630
Web address : https://doi.org/10.1016/j.biopha.2023.115630
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/181463966
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 a major role in cancers, treatment effect monitoring using copy-number profiles has received limited attention as compared to mutations. A major reason for this is the insensitivity of CNA analysis for the real-life tumor-fraction ctDNA samples. We performed copy-number analysis on 152 plasma samples obtained from 29 patients with high-grade serous ovarian cancer (HGSC) using a sequencing panel targeting over 500 genes. Twenty-one patients had temporally matched tissue and plasma sample pairs, which enabled assessing concordance with tissues sequenced with the same panel or whole-genome sequencing and to evaluate sensitivity. Our approach could detect concordant CNA profiles in most plasma samples with as low as 5% tumor content and highly amplified regions in samples with ∼1% of tumor content. Longitudinal profiles showed changes in the CNA profiles in seven out of 11 patients with high tumor-content plasma samples at relapse. These changes included focal acquired or lost copy-numbers, even though most of the genome remained stable. Two patients displayed major copy-number profile changes during therapy. Our analysis revealed ctDNA-detectable subclonal selection resulting from both surgical operations and chemotherapy. Overall, longitudinal ctDNA data showed acquired and diminished CNAs at relapse when compared to pre-treatment samples. These results highlight the importance of genomic profiling during treatment as well as underline the usability of ctDNA.
Downloadable publication This is an electronic reprint of the original article. |  |
