ctDNA detectability and representativeness in seven body liquids from patients with metastatic breast cancer
Liquid biopsies enable non-invasive monitoring and characterization of metastatic cancer, primarily through circulating tumor DNA (ctDNA) in blood. The representativeness of all metastatic sites in these liquid biopsies and the clinical relevance of other body fluids remain uncertain. We performed low-pass whole genome sequencing on 216 liquid and 745 metastatic tissue samples from 20 autopsied female patients with metastatic breast cancer to assess ctDNA detection, fraction, and site representativeness in seven body fluids (blood, ascites, cerebrospinal fluid, pericardial fluid, pleural fluid, saliva, and urine). Complementarily, whole exome sequencing on 86 liquid samples from 11 patients explored mutational information. ctDNA was detected in all fluids, but most frequently in blood, followed by ascites, pleural fluid, and cerebrospinal fluid. Phylogenetic reconstruction indicated that site representativeness varies by fluid type. Mutational and gene-level copy number analyses revealed clinically relevant information unique to non-blood fluids. These findings suggest a multi-fluid approach could enhance metastatic cancer monitoring and characterization.
Authors
- Ha-Linh Nguyen (ORCID: https://orcid.org/0000-0002-2538-7657)
- Patrick Neven (ORCID: https://orcid.org/0000-0002-1434-9460)
- Hava Izci (ORCID: https://orcid.org/0000-0002-3344-0198)
- Kristien Borremans (ORCID: https://orcid.org/0000-0001-7047-1543)
- Marion Maetens (ORCID: https://orcid.org/0000-0002-0505-2622)
- Anirudh Pabba (ORCID: https://orcid.org/0000-0003-2002-6956)
- Amena Mahdami (ORCID: https://orcid.org/0000-0002-3226-6933)
- Jonas Demeulemeester (ORCID: https://orcid.org/0000-0002-2660-2478)
- Imane Bachir
- Josephine Van Cauwenberge (ORCID: https://orcid.org/0000-0001-9802-186X)
- Madita Nysen
- Sophia Leduc (ORCID: https://orcid.org/0000-0002-4931-1999)
- Evy Vanderheyden
- François Richard (ORCID: https://orcid.org/0000-0003-4353-3619)
- Elia Mario Biganzoli (ORCID: https://orcid.org/0000-0003-1202-5873)
- Christine Desmedt (ORCID: https://orcid.org/0000-0002-5223-5579)
- Maxim De Schepper (ORCID: https://orcid.org/0000-0001-9829-8535)
- Hans Wildiers (ORCID: https://orcid.org/0000-0001-8990-7837)
- Karen Van Baelen (ORCID: https://orcid.org/0000-0002-5700-3574)
- Gitte Zels (ORCID: https://orcid.org/0000-0002-6332-3830)
- Tatjana Geukens (ORCID: https://orcid.org/0000-0001-8828-8739)
- Giuseppe Floris (ORCID: https://orcid.org/0000-0003-2391-5425)
- Diether Lambrechts (ORCID: https://orcid.org/0000-0002-3429-302X)
- Bram Boeckx (ORCID: https://orcid.org/0000-0002-0296-6680)
- Thomas Van Brussel (ORCID: https://orcid.org/0000-0002-1706-8381)
- E. Rousseau
- Wouter Van Den Bogaert (ORCID: https://orcid.org/0000-0002-5803-3409)
- Sigrid Hatse (ORCID: https://orcid.org/0000-0002-6764-2628)
- Peter Vermeulen
- C. Carette (ORCID: https://orcid.org/0009-0006-7921-212X)
Institutions
- University of Milan (IT)
- Breast Cancer Research Foundation (US)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Ziekenhuisnetwerk Antwerpen Stuivenberg (BE)
- Cell and Tissue Systems (United States) (US)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1038/s41467-025-65838-1
- Citations
- 1
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Breast Cancer Research Foundation
- Breast Cancer Alliance
- American Society of Clinical Oncology
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- Vlaamse regering