Comparative analysis of capture methods for genomic profiling of circulating tumor cells in colorectal cancer

The genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. Here, we contrasted the genomic profiles of CTC pools recovered from metastatic colorectal cancer (mCRC) patients using...

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Published in:Genomics (San Diego, Calif.) Calif.), 2022-11, Vol.114 (6), p.110500-110500, Article 110500
Main Authors: Alves, Joao M., Estévez-Gómez, Nuria, Valecha, Monica, Prado-López, Sonia, Tomás, Laura, Alvariño, Pilar, Piñeiro, Roberto, Muinelo-Romay, Laura, Mondelo-Macía, Patricia, Salgado, Mercedes, Iglesias-Gómez, Agueda, Codesido-Prada, Laura, Cubiella, Joaquin, Posada, David
Format: Article
Language:English
Subjects:
Circulating tumor cells
Colorectal cancer
Colorectal Neoplasms - genetics
Genomics
Humans
Intratumor genomic heterogeneity
Liquid biopsy
Neoplastic Cells, Circulating
Precision medicine
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Summary:The genomic profiling of circulating tumor cells (CTCs) in the bloodstream should provide clinically relevant information on therapeutic efficacy and help predict cancer survival. Here, we contrasted the genomic profiles of CTC pools recovered from metastatic colorectal cancer (mCRC) patients using different enrichment strategies (CellSearch, Parsortix, and FACS). Mutations inferred in the CTC pools differed depending on the enrichment strategy and, in all cases, represented a subset of the mutations detected in the matched primary tumor samples. However, the CTC pools from Parsortix, and in part, CellSearch, showed diversity estimates, mutational signatures, and drug-suitability scores remarkably close to those found in matching primary tumor samples. In addition, FACS CTC pools were enriched in apparent sequencing artifacts, leading to much higher genomic diversity estimates. Our results highlight the utility of CTCs to assess the genomic heterogeneity of individual tumors and help clinicians prioritize drugs in mCRC. •We have found substantial differences in the mutational loads of CTC pools obtained using different CTC-capture methods.•CTC pools from Parsortix returned similar intratumor heterogeneity estimates compared to those found in matching primary tumors.•CTC-derived genomic data appears to offer reliable information for prioritizing therapeutic strategies in colorectal cancer.
ISSN:0888-7543
1089-8646
DOI:10.1016/j.ygeno.2022.110500