Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing.

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Circulating tumor cells (CTCs) reflect dynamic tumor genotypes.
• Monitoring genetic changes in cancer is crucial for effective treatment.

Purpose of the Study:

• To perform comprehensive genomic profiling of CTCs.
• To compare genetic mutations in CTCs with primary tumors and metastases.
• To establish CTCs as a liquid biopsy for cancer monitoring.

Main Methods:

• Utilized array-comparative genomic hybridization (CGH) and next-generation sequencing.
• Employed the CellSearch system for CTC detection in stage IV colorectal carcinoma patients.
• Performed massive parallel sequencing on CTCs, primary tumors, and metastases.

Main Results:

• Detected colorectal cancer-associated copy number changes in isolated CTCs, often shared with primary tumors.
• Found mutations in known driver genes (APC, KRAS, PIK3CA) in CTCs that were also present in primary tumors and metastases.
• Identified mutations exclusively in CTCs, which were mostly present at subclonal levels in primary tumors/metastases.

Conclusions:

• CTCs harbor genetic alterations mirroring those in primary tumors and metastases.
• CTCs can serve as a valuable non-invasive liquid biopsy for tracking tumor evolution.
• This approach offers enhanced options for monitoring cancer progression, treatment response, and relapse.