Novel strategies for circulating tumor cell analysis in glioblastoma

Glioblastoma (GBM) is an aggressive brain tumor characterized by marked intra- and inter-tumoral heterogeneity and inevitable recurrence. Although extracranial metastasis is rare, circulating tumor cells (CTCs) are consistently detected in GBM patients, suggesting their potential as liquid biopsy biomarkers.

Lessi's team established and optimized a workflow that combines physical enrichment with the Parsortix system and single-cell isolation using the DEPArray NxT platform, enabling the genomic and phenotypic characterization of both bulk and single CTCs. In a cohort of 27 GBM patients, whole-exome sequencing (WES) confirmed that CTCs share somatic mutations and copy number alterations (CNAs) with matched primary and recurrent tumors, proving their tumor origin. CTCs were significantly more abundant in primary compared to recurrent GBM, and absent in radionecrosis and lymphoma cases, establishing a diagnostic cutoff of 4 CTCs per 5 mL of blood. Single-cell analyses revealed striking heterogeneity, including CTCs lacking detectable CNAs. Similar CNA-negative populations were also observed in scRNA-seq data from GBM cell lines, suggesting the coexistence of malignant and tumor microenvironment–derived cells in circulation.

Beyond GBM, the team applied the same Parsortix–DEPArray pipeline to pediatric osteosarcoma (OS) patients. Here, they identified both mesenchymal-like and epithelial-like CTC subpopulations, with longitudinal tracking of epithelial-like CTCs correlating with chemotherapy response. These results underscore the versatility and translational relevance of their workflow across distinct tumor types, paving the way for the development of personalized liquid biopsy strategies.

Why join this webinar?

• Discover how circulating tumor cells (CTCs) can serve as powerful liquid biopsy biomarkers in glioblastoma.
• Learn about an innovative workflow combining Parsortix® and DEPArray technologies for CTC analysis.
• Understand how CTCs reflect tumor mutations and heterogeneity at the single-cell level.
• See the importance of analyzing bulk CTCs enriched with the Parsortix system to obtain comprehensive tumor information (e.g., whole-exome data) without the need for whole genome amplification.
• Explore how the same applications are extended to pediatric osteosarcoma, a highly aggressive tumor