The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
A Big Bang model of human colorectal tumor growth
Open accessAbstract
What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.
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Cites
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Clonal heterogeneity and tumor evolution: past, present, and the future
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From tumour heterogeneity to advances in precision treatment of colorectal cancer
Punt, C. J. A., Koopman, M., & Vermeulen, L. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.171 · Cited by 654
Telomeres: history, health, and hallmarks of aging
Chakravarti, D., LaBella, K. A., & DePinho, R. A. (2021) · Cell · doi:10.1016/j.cell.2020.12.028 · Cited by 637
The lingering mysteries of metastatic recurrence in breast cancer
Riggio, A. I., Varley, K. E., & Welm, A. L. (2021) · British Journal of Cancer · doi:10.1038/s41416-020-01161-4 · Cited by 616
Metadata
- Authors
- Sottoriva, A., Kang, H., Ma, Z., Graham, T. A., Salomon, M. P., Zhao, J., Marjoram, P., Siegmund, K., Press, M. F., Shibata, D., & Curtis, C.
- Venue
- Nature Genetics
- Published
- 2015-02-09
- Volume
- 47
- Issue
- 3
- Pages
- 209-216
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2010873488
- Cited by
- 1,015
- References
- 55
- FWCI
- 35.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Sottoriva, A., Kang, H., Ma, Z., Graham, T. A., Salomon, M. P., Zhao, J., Marjoram, P., Siegmund, K., Press, M. F., Shibata, D., & Curtis, C. (2015). A Big Bang model of human colorectal tumor growth. Nature Genetics. https://doi.org/10.1038/ng.3214
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