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Cancer archetypes co-opt and adapt the transcriptional programs of existing cellular states

Maayan Baron, Isabella S. Kim, Reuben Moncada, Yun Yan, Nathaniel R. Campbell, Richard M. White, Itai Yanai
doi: https://doi.org/10.1101/396622
Maayan Baron
1Institute for Computational Medicine, NYU School of Medicine, New York, NY USA
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Isabella S. Kim
2Cancer Biology & Genetics, Memorial Sloan Kettering Cancer Center, New York, NY USA
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Reuben Moncada
1Institute for Computational Medicine, NYU School of Medicine, New York, NY USA
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Yun Yan
1Institute for Computational Medicine, NYU School of Medicine, New York, NY USA
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Nathaniel R. Campbell
3Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, Memorial Sloan Kettering Cancer Center, New York, NY USA
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Richard M. White
2Cancer Biology & Genetics, Memorial Sloan Kettering Cancer Center, New York, NY USA
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Itai Yanai
1Institute for Computational Medicine, NYU School of Medicine, New York, NY USA
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  • For correspondence: itai.yanai@nyumc.org
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ABSTRACT

Tumors evolve as independent systems comprising complex survival-ensuring functions, however the nature of these distinct processes and their recurrence across cancers is not clear. Here we propose that melanoma cancer-cells can be classified to three ‘archetypes’ that co-opt the neural crest, mature melanocytes, and stress gene expression programs, respectively, have a unique subclonal structure, and are conserved between zebrafish and human melanomas. Studying the natural history of a zebrafish melanoma tumor at the single-cell level, we found that one archetype exclusively exhibits the signature of the Warburg effect, suggesting that a shifting balance in energy production occurs differentially in the tumor. Deconvolving bulk human melanomas, we found that patients with a dominant fraction of the neural crest archetype show worse survival rates, indicating a clinical relevance for the composition of archetypes. Finally, we provide evidence that extending our approach to other cancer types can reveal universal and cancer-specific archetypes.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 22, 2018.
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Cancer archetypes co-opt and adapt the transcriptional programs of existing cellular states
Maayan Baron, Isabella S. Kim, Reuben Moncada, Yun Yan, Nathaniel R. Campbell, Richard M. White, Itai Yanai
bioRxiv 396622; doi: https://doi.org/10.1101/396622
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Cancer archetypes co-opt and adapt the transcriptional programs of existing cellular states
Maayan Baron, Isabella S. Kim, Reuben Moncada, Yun Yan, Nathaniel R. Campbell, Richard M. White, Itai Yanai
bioRxiv 396622; doi: https://doi.org/10.1101/396622

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