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Clonal dominance defines metastatic dissemination in pancreatic cancer

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Item Type:Article
Title:Clonal dominance defines metastatic dissemination in pancreatic cancer
Creators Name:Ho, I.L. and Li, C.Y. and Wang, F. and Zhao, L. and Liu, J. and Yen, E.Y. and Dyke, C.A. and Shah, R. and Liu, Z. and Çetin, A.O. and Chu, Y. and Citron, F. and Attanasio, S. and Corti, D. and Darbaniyan, F. and Del Poggetto, E. and Loponte, S. and Liu, J. and Soeung, M. and Chen, Z. and Jiang, S. and Jiang, H. and Inoue, A. and Gao, S. and Deem, A. and Feng, N. and Ying, H. and Kim, M. and Giuliani, V. and Genovese, G. and Zhang, J. and Futreal, A. and Maitra, A. and Heffernan, T. and Wang, L. and Do, K.A. and Gargiulo, G. and Draetta, G. and Carugo, A. and Lin, R. and Viale, A.
Abstract:Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination. This model revealed the multifaceted nature of tumor growth, with rapid changes in clonal fitness leading to continuous reshuffling of tumor architecture and alternating clonal dominance as a distinct feature of cancer growth. Regarding dissemination, a large fraction of tumor lineages could be found at secondary sites each having distinctive organ growth patterns as well as numerous undescribed behaviors such as abortive colonization. Paired analysis of primary and secondary sites revealed fitness as major contributor to dissemination. From the analysis of pro- and nonmetastatic isogenic subclones, we identified a transcriptomic signature able to identify metastatic cells in human tumors and predict patients' survival.
Keywords:Ecosystem, Gene Expression Profiling, Pancreatic Neoplasms, Transcriptome
Source:Science Advances
Publisher:American Association for the Advancement of Science
Page Range:eadd9342
Date:15 March 2024
Official Publication:https://doi.org/10.1126/sciadv.add9342
PubMed:View item in PubMed

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