Clonal dominance defines metastatic dissemination in pancreatic cancer

I. Lin Ho, Chieh Yuan Li, Fuchenchu Wang, Li Zhao, Jingjing Liu, Er Yen Yen, Charles A. Dyke, Rutvi Shah, Zhaoliang Liu, Ali Osman Çetin, Yanshuo Chu, Francesca Citron, Sergio Attanasio, Denise Corti, Faezeh Darbaniyan, Edoardo Del Poggetto, Sara Loponte, Jintan Liu, Melinda Soeung, Ziheng ChenShan Jiang, Hong Jiang, Akira Inoue, Sisi Gao, Angela Deem, Ningping Feng, Haoqiang Ying, Michael Kim, Virginia Giuliani, Giannicola Genovese, Jianhua Zhang, Andrew Futreal, Anirban Maitra, Timothy Heffernan, Linghua Wang, Kim Anh Do, Gaetano Gargiulo, Giulio Draetta, Alessandro Carugo, Ruitao Lin, Andrea Viale

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article numbereadd9342
JournalScience Advances
Volume10
Issue number11
DOIs
StatePublished - Mar 15 2024

ASJC Scopus subject areas

  • General

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