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Tumor diversity and the trade-off between universal cancer tasks

Recent advances have enabled powerful methods to sort tumors into prognosis and treatment groups. We are still missing, however, a general theoretical framework to understand the vast diversity of tumor gene expression and mutations. Here we present a framework based on multi-task evolution theory,...

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Detalles Bibliográficos
Autores principales: Hausser, Jean, Szekely, Pablo, Bar, Noam, Zimmer, Anat, Sheftel, Hila, Caldas, Carlos, Alon, Uri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882839/
https://www.ncbi.nlm.nih.gov/pubmed/31780652
http://dx.doi.org/10.1038/s41467-019-13195-1
Descripción
Sumario:Recent advances have enabled powerful methods to sort tumors into prognosis and treatment groups. We are still missing, however, a general theoretical framework to understand the vast diversity of tumor gene expression and mutations. Here we present a framework based on multi-task evolution theory, using the fact that tumors need to perform multiple tasks that contribute to their fitness. We find that trade-offs between tasks constrain tumor gene-expression to a continuum bounded by a polyhedron whose vertices are gene-expression profiles, each specializing in one task. We find five universal cancer tasks across tissue-types: cell-division, biomass and energy, lipogenesis, immune-interaction and invasion and tissue-remodeling. Tumors that specialize in a task are sensitive to drugs that interfere with this task. Driver, but not passenger, mutations tune gene-expression towards specialization in specific tasks. This approach can integrate additional types of molecular data into a framework of tumor diversity grounded in evolutionary theory.