Journal: Nature communications
This study examined how well different body fluids reflect the genomic landscape of metastatic breast cancer at autopsy.
Design and methods
- • Included 20 women with metastatic breast cancer undergoing rapid autopsy.
- • Analyzed 216 liquid samples and 745 metastatic tissue samples.
- • Performed low-pass whole-genome sequencing on seven fluids: blood, ascites, cerebrospinal fluid (CSF), pericardial fluid, pleural fluid, saliva, and urine.
- • Performed whole-exome sequencing on 86 liquid samples from a subset of 11 patients to characterize mutations.
Key findings
- • Circulating tumor DNA (ctDNA) was detectable in all assessed fluid types.
- • Blood most consistently contained ctDNA, followed by ascites, pleural fluid, and CSF.
- • Phylogenetic analyses showed that different fluids vary in how well they represent all metastatic sites; no single fluid uniformly captured the entire metastatic landscape.
- • Mutational and gene-level copy number analyses from non-blood fluids sometimes revealed clinically relevant alterations that were not evident in blood.
Implications
- • Blood remains the most reliable and broadly applicable liquid biopsy source.
- • However, non-blood fluids—particularly those in anatomic proximity to certain metastatic sites—can provide additional, unique genomic information.
- • A multi-fluid liquid biopsy strategy could improve characterization and monitoring of metastatic disease beyond what is achievable using blood alone.