The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Pancreatic Cancer Metastases Harbor Evidence of Polyclonality
Open accessAbstract
Studies of the cancer genome have demonstrated that tumors are composed of multiple subclones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these subclones. To understand the cellular dynamics that drive metastasis, we used multicolor lineage-tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity decreases during premalignant progression. Furthermore, we present evidence that a significant fraction of metastases are polyclonally seeded by distinct tumor subclones. Finally, we show that clonality during metastatic growth—leading to either monoclonal or polyclonal expansion—differs based on the site of metastatic invasion. These results provide an unprecedented window into the cellular dynamics of tumor evolution and suggest that heterotypic interactions between tumor subpopulations contribute to metastatic progression in native tumors. Significance: Studies of tumor heterogeneity indicate that distinct tumor subclones interact during cancer progression. Here, we demonstrate by lineage tracing that metastases often involve seeding by more than one clone and that subsequent cellular outgrowth depends on the metastatic site. These findings provide insight into clonal diversity and evolution in metastatic disease. Cancer Discov; 5(10); 1086–97. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 1005
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Cites
Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774 · cited 1×
“In human cancers, subclones are defined genetically as distinct tumor populations that share a set of identical founder mutations (2, 11, 20).”
BackgroundGreaves, M., & Maley, C. C. (2012) · Nature · doi:10.1038/nature10762 · Cited by 3,162
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
Tumor Self-Seeding by Circulating Cancer Cells
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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
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Cited by
Tumour heterogeneity and resistance to cancer therapies
Dagogo-Jack, I., & Shaw, A. T. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.166 · Cited by 3,846
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840
Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth
Zhang, L., Zhang, S., Yao, J., Lowery, F. J., Zhang, Q., Huang, W.-C., Li, P., Li, M., Wang, X., Zhang, C., et al. (2015) · Nature · doi:10.1038/nature15376 · Cited by 1,175
Hezaveh, K., Shinde, R. S., Klötgen, A., Halaby, M. J., Lamorte, S., Ciudad, M. T., Quevedo, R., Neufeld, L., Liu, Z. Q., Jin, R., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.01.006 · Cited by 746
EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration
Aiello, N. M., Maddipati, R., Norgard, R. J., Balli, D., Li, J., Yuan, S., Yamazoe, T., Black, T., Sahmoud, A., Furth, E. E., et al. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.05.027 · Cited by 707
Self-citation
Metadata
- Authors
- Maddipati, R., & Stanger, B. Z.
- Venue
- Cancer Discovery
- Published
- 2015-09-30
- Volume
- 5
- Issue
- 10
- Pages
- 1086-1097
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2170858024
- Cited by
- 298
- References
- 6
- FWCI
- 7.95
- Type
- journal article
- Language
- en
- Open access
- green
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