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Low-pass whole genome sequencing of circulating tumor cells to evaluate chromosomal instability in triple-negative breast cancer

Authors :
Serena Di Cosimo
Marco Silvestri
Cinzia De Marco
Alessia Calzoni
Maria Carmen De Santis
Maria Grazia Carnevale
Carolina Reduzzi
Massimo Cristofanilli
Vera Cappelletti
Source :
Scientific Reports, Vol 14, Iss 1, Pp 1-8 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract Chromosomal Instability (CIN) is a common and evolving feature in breast cancer. Large-scale Transitions (LSTs), defined as chromosomal breakages leading to gains or losses of at least 10 Mb, have recently emerged as a metric of CIN due to their standardized definition across platforms. Herein, we report the feasibility of using low-pass Whole Genome Sequencing to assess LSTs, copy number alterations (CNAs) and their relationship in individual circulating tumor cells (CTCs) of triple-negative breast cancer (TNBC) patients. Initial assessment of LSTs in breast cancer cell lines consistently showed wide-ranging values (median 22, range 4–33, mean 21), indicating heterogeneous CIN. Subsequent analysis of CTCs revealed LST values (median 3, range 0–18, mean 5), particularly low during treatment, suggesting temporal changes in CIN levels. CNAs averaged 30 (range 5–49), with loss being predominant. As expected, CTCs with higher LSTs values exhibited increased CNAs. A CNA-based classifier of individual patient-derived CTCs, developed using machine learning, identified genes associated with both DNA proliferation and repair, such as RB1, MYC, and EXO1, as significant predictors of CIN. The model demonstrated a high predictive accuracy with an Area Under the Curve (AUC) of 0.89. Overall, these findings suggest that sequencing CTCs holds the potential to facilitate CIN evaluation and provide insights into its dynamic nature over time, with potential implications for monitoring TNBC progression through iterative assessments.

Details

Language :
English
ISSN :
20452322
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.5e21cc35fec64b789fb53b1caf488296
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-024-71378-3