The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
Quantitative evidence for early metastatic seeding in colorectal cancer
Open accessAbstract
Both the timing and molecular determinants of metastasis are unknown, hindering treatment and prevention efforts. Here we characterize the evolutionary dynamics of this lethal process by analyzing exome-sequencing data from 118 biopsies from 23 patients with colorectal cancer with metastases to the liver or brain. The data show that the genomic divergence between the primary tumor and metastasis is low and that canonical driver genes were acquired early. Analysis within a spatial tumor growth model and statistical inference framework indicates that early disseminated cells commonly (81%, 17 out of 21 evaluable patients) seed metastases while the carcinoma is clinically undetectable (typically, less than 0.01 cm3). We validated the association between early drivers and metastasis in an independent cohort of 2,751 colorectal cancers, demonstrating their utility as biomarkers of metastasis. This conceptual and analytical framework provides quantitative in vivo evidence that systemic spread can occur early in colorectal cancer and illuminates strategies for patient stratification and therapeutic targeting of the canonical drivers of tumorigenesis. Analysis of evolutionary dynamics of colorectal cancers and paired distant brain or liver metastases provides evidence that early disseminated cancer cells seed metastases before the carcinoma is clinically detectable.
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Cites
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Cited by
Crosby, D., Bhatia, S., Brindle, K. M., Coussens, L. M., Dive, C., Emberton, M., Esener, S., Fitzgerald, R. C., Gambhir, S. S., Kuhn, P., et al. (2022) · Science · doi:10.1126/science.aay9040 · Cited by 1,379
Gerstberger, S., Jiang, Q., & Ganesh, K. (2023) · Cell · doi:10.1016/j.cell.2023.03.003 · Cited by 913
Genetic and biological hallmarks of colorectal cancer
Li, J., Ma, X., Chakravarti, D., Shalapour, S., & DePinho, R. A. (2021) · Genes & Development · doi:10.1101/gad.348226.120 · Cited by 573
Brain malignancies: Glioblastoma and brain metastases
Lah, T. T., Novak, M., & Breznik, B. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.10.010 · Cited by 438
Emerging role of tumor cell plasticity in modifying therapeutic response
Qin, S., Jiang, J., Lu, Y., Nice, E. C., Huang, C., Zhang, J., & He, W. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00313-5 · Cited by 268
Metadata
- Authors
- Hu, Z., Ding, J., Ma, Z., Sun, R., Seoane, J. A., Scott Shaffer, J., Suarez, C. J., Berghoff, A. S., Cremolini, C., Falcone, A., Loupakis, F., Birner, P., Preusser, M., Lenz, H.-J., & Curtis, C.
- Venue
- Nature Genetics
- Published
- 2019-06-17
- Volume
- 51
- Issue
- 7
- Pages
- 1113-1122
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2950945543
- Cited by
- 490
- References
- 83
- FWCI
- 19.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Hu, Z., Ding, J., Ma, Z., Sun, R., Seoane, J. A., Scott Shaffer, J., Suarez, C. J., Berghoff, A. S., Cremolini, C., Falcone, A., Loupakis, F., Birner, P., Preusser, M., Lenz, H.-J., & Curtis, C. (2019). Quantitative evidence for early metastatic seeding in colorectal cancer. Nature Genetics. https://doi.org/10.1038/s41588-019-0423-x
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