Genetic analysis of heterogeneous subsets of circulating tumour cells from high grade serous ovarian carcinoma patients

Authors

Du-Bois Asante, Edith Cowan University
Ganendra R. K. A. Mohan
Emmanuel Acheampong, Edith Cowan UniversityFollow
Mel R. Ziman Dr, Edith Cowan UniversityFollow
Leslie Calapre, Edith Cowan UniversityFollow
Tarek M. Meniawy, Edith Cowan UniversityFollow
Elin S. Gray, Edith Cowan UniversityFollow
Aaron B. Beasley, Edith Cowan UniversityFollow

Document Type

Journal Article

Publication Title

Scientific Reports

Publisher

Springer Nature

School

School of Medical and Health Sciences / Centre for Precision Health

RAS ID

54556

Funders

Edith Cowan University

Cancer Council Western Australia

Australia New Zealand Gynaecological Oncology Group

Comments

Asante, D. B., Mohan, G. R. K. A., Acheampong, E., Ziman, M., Calapre, L., Meniawy, T. M., . . . Beasley, A. B. (2023). Genetic analysis of heterogeneous subsets of circulating tumour cells from high grade serous ovarian carcinoma patients. Scientific Reports, 13, article 2552. https://doi.org/10.1038/s41598-023-29416-z

Abstract

Circulating tumour cells (CTCs) are heterogenous and contain genetic information from the tumour of origin. They bear specific intra- and extra-cellular protein markers aiding in their detection. However, since these markers may be shared with other rare cells in the blood, only genetic testing can confirm their malignancy. Herein, we analyse different CTC subsets using single cell whole genome DNA sequencing to validate their malignant origin. We randomly selected putative CTCs identified by immunostaining that were isolated from 4 patients with high grade serous ovarian cancer (HGSOC) and one with benign cystadenoma. We specifically targeted CTCs positive for epithelial (CK/EpCAM^pos), mesenchymal (vimentin^pos), and pseudoendothelial (CK/EpCAM^pos plus CD31^pos) markers. We isolated these cells and performed whole genome amplification (WGA) and low-pass whole-genome sequencing (LP-WGS) for analysis of copy number alterations (CNA). Of the CK/EpCAM^pos cells analysed from the HGSOC patients, 2 of 3 cells showed diverse chromosomal CNAs. However, the 4 pseudoendothelial cells (CK/EpCAM^pos plus CD31^pos) observed in the HGSOC cases did not carry any CNA. Lastly, two of the clusters of vimentin positive cells sequenced from those found in the benign cystadenoma case had CNA. Despite the low number of cells analysed, our results underscore the importance of genetic analysis of putative CTCs to confirm their neoplastic origin. In particular, it highlights the presence of a population of CK/EpCAM^pos cells that are not tumour cells in patients with HGSOC, which otherwise would be counted as CTCs.

DOI

10.1038/s41598-023-29416-z

Related Publications

Asante, D. (2022). Development and evaluation of methodologies for analysis of CTC and ctDNA in patients with ovarian carcinoma. https://ro.ecu.edu.au/theses/2570

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This work is licensed under a Creative Commons Attribution 4.0 License.