Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types
Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expecte...
| Autores: | , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | Universitat Pompeu Fabra |
| Repositório: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/25106 |
| Acesso em linha: | http://hdl.handle.net/10230/25106 http://dx.doi.org/10.15252/msb.20156102 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Genètica molecular Càncer Cancer Epistasis Evolution Genetic interaction networks Tissue specificity |
| Resumo: | Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another. |
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