APA
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Alves, J., Prado-López, S., Tomás, L., Valecha, M., Estévez-Gómez, N., Alvariño, P., … Posada, D. (2022). Clonality and timing of relapsing colorectal cancer metastasis revealed through whole-genome single-cell sequencing. Cancer Letters, 543.
Chicago/Turabian
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Alves, J., S. Prado-López, L. Tomás, M. Valecha, N. Estévez-Gómez, P. Alvariño, Dominik Geissel, et al. “Clonality and Timing of Relapsing Colorectal Cancer Metastasis Revealed through Whole-Genome Single-Cell Sequencing.” Cancer Letters 543 (2022).
MLA
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Alves, J., et al. “Clonality and Timing of Relapsing Colorectal Cancer Metastasis Revealed through Whole-Genome Single-Cell Sequencing.” Cancer Letters, vol. 543, 2022.
BibTeX Click to copy
@article{j2022a,
title = {Clonality and timing of relapsing colorectal cancer metastasis revealed through whole-genome single-cell sequencing},
year = {2022},
journal = {Cancer Letters},
volume = {543},
author = {Alves, J. and Prado-López, S. and Tomás, L. and Valecha, M. and Estévez-Gómez, N. and Alvariño, P. and Geissel, Dominik and Modest, D. and Sauer, I. and Pratschke, J. and Raschzok, N. and Sers, C. and Mamlouk, S. and Posada, D.}
}
BACKGROUND: Recurrence of tumor cells following local and systemic therapy is a significant hurdle in cancer. Most patients with metastatic colorectal cancer (mCRC) will relapse, despite resectioning the metastatic lesions. A better understanding of the evolutionary history of recurrent lesions is thus required to identify the spatial and temporal patterns of metastatic progression and expose the genetic determinants of therapeutic resistance. METHODS: Utilizing a robust Bayesian phylogenetic approach, we analyzed a unique single-cell whole-genome sequencing dataset comprising 60 cells sampled from metastatic and recurrent hepatic lesions of a patient with a long-term disease course to investigate the origin, timing, and clonality of a colorectal metastatic relapse. We further tracked the changes in the size of the malignant cell population and evaluated the impact of the treatment strategy on the mutational landscape of this tumor. RESULTS: Our results suggest that the recurrent lesion originated from the clonal expansion of a single drug-resistant metastatic lineage, which began to expand around one year before surgical resection of the relapse. We additionally observed substantial variability in the substitution rates along the tumor cell phylogeny and found a large number of mutations specific to the ancestral lineage that gave rise to the relapse, including non-silent mutations in CRC genes. Moreover, our results point to a substantial contribution of chemotherapy exposure to the overall mutational burden. CONCLUSIONS: Our study suggests that resistant colorectal metastatic clones can quickly grow, even under strong drug-imposed pressure, highlighting the importance of profiling the genomic landscape of tumor lesions to identify mutations potentially contributing to treatment failure.
