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Clonal competition with alternating dominance in multiple myeloma
Open accessAbstract
Emerging evidence indicates that tumors can follow several evolutionary paths over a patient's disease course. With the use of serial genomic analysis of samples collected at different points during the disease course of 28 patients with multiple myeloma, we found that the genomes of standard-risk patients show few changes over time, whereas those of cytogenetically high-risk patients show significantly more changes over time. The results indicate the existence of 3 temporal tumor types, which can either be genetically stable, linearly evolving, or heterogeneous clonal mixtures with shifting predominant clones. A detailed analysis of one high-risk patient sampled at 7 time points over the entire disease course identified 2 competing subclones that alternate in a back and forth manner for dominance with therapy until one clone underwent a dramatic linear evolution. With the use of the Vk*MYC genetically engineered mouse model of myeloma we modeled this competition between subclones for predominance occurring spontaneously and with therapeutic selection.
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Cites
Distant metastasis occurs late during the genetic evolution of pancreatic cancer
Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., et al. (2010) · Nature · doi:10.1038/nature09515 · Cited by 2,502
The patterns and dynamics of genomic instability in metastatic pancreatic cancer
Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., et al. (2010) · Nature · doi:10.1038/nature09460 · Cited by 1,317
Cited by
The causes and consequences of genetic heterogeneity in cancer evolution
Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013) · Nature · doi:10.1038/nature12625 · Cited by 2,262
Biological and therapeutic impact of intratumor heterogeneity in cancer evolution
McGranahan, N., & Swanton, C. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.12.001 · Cited by 1,077
Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy
Lohr, J. G., Stojanov, P., Carter, S. L., Cruz-Gordillo, P., Lawrence, M. S., Auclair, D., Sougnez, C., Knoechel, B., Gould, J., Saksena, G., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2013.12.015 · Cited by 988
Self-citationIntratumor Heterogeneity: Evolution through Space and Time
Swanton, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2217 · Cited by 931
Heterogeneity of genomic evolution and mutational profiles in multiple myeloma
Bolli, N., Avet-Loiseau, H., Wedge, D. C., Van Loo, P., Alexandrov, L. B., Martincorena, I., Dawson, K. J., Iorio, F., Nik-Zainal, S., Bignell, G. R., et al. (2014) · Nature Communications · doi:10.1038/ncomms3997 · Cited by 875
Metadata
- Authors
- Keats, J. J., Chesi, M., Egan, J. B., Garbitt, V. M., Palmer, S. E., Braggio, E., Van Wier, S., Blackburn, P. R., Baker, A. S., Dispenzieri, A., Kumar, S., Rajkumar, S. V., Carpten, J. D., Barrett, M., Fonseca, R., Stewart, A. K., & Bergsagel, P. L.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-08-02
- Volume
- 120
- Issue
- 5
- Pages
- 1067-1076
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2055662838
- Cited by
- 637
- References
- 2
- FWCI
- 43.60
- Type
- journal article
- Language
- en
- Open access
- green
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