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Circuits of cancer drivers revealed by convergent misregulation of transcription factor targets across tumor types

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dc.contributor.author González-Pérez, Abel
dc.date.accessioned 2016-06-08T10:07:01Z
dc.date.available 2016-06-08T10:07:01Z
dc.date.issued 2016
dc.identifier.citation Gonzalez P. Circuits of cancer drivers revealed by convergent misregulation of transcription factor targets across tumor types. Genome Medicine. 2016; 8(1): 6. DOI:10.1186/s13073-015-0260-1
dc.identifier.issn 1756-994X
dc.identifier.uri http://hdl.handle.net/10230/26867
dc.description.abstract BACKGROUND: Large tumor genome sequencing projects have now uncovered a few hundred genes involved in the onset of tumorigenesis, or drivers, in some two dozen malignancies. One of the main challenges emerging from this catalog of drivers is how to make sense of their heterogeneity in most cancer types. This is key not only to understand how carcinogenesis appears and develops in these malignancies to be able to early diagnose them, but also to open up the possibility to employ therapeutic strategies targeting a driver protein to counteract the alteration of another connected driver. METHODS: Here, I focus on driver transcription factors and their connection to tumorigensis in several tumor types through the alteration of the expression of their targets. First, I explore their involvement in tumorigenesis as mutational drivers in 28 different tumor types. Then, I collect a list of downstream targets of the all driver transcription factors (TFs), and identify which of them exhibit a differential expression upon alterations of driver transcription factors. RESULTS: /nI identify the subset of targets of each TF most likely mediating the tumorigenic effect of their driver alterations in each tumor type, and explore their overlap. Furthermore, I am able to identify other driver genes that cause tumorigenesis through the alteration of very similar sets of targets./nCONCLUSIONS: I thus uncover these circuits of connected drivers which cause tumorigenesis through the perturbation of overlapping cellular pathways in a pan-cancer manner across 15 malignancies. The systematic detection of these circuits may be key to propose novel therapeutic strategies indirectly targeting driver alterations in tumors.
dc.description.sponsorship AG-P is supported by a Ramon y Cajal scholarship funded by the Spanish Ministry of Economy
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.rights © Abel González-Pérez 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author and the source, provide a link to the Creative Commons license, and indicate if changes were made
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Tumors
dc.subject.other Càncer
dc.subject.other Genomes
dc.title Circuits of cancer drivers revealed by convergent misregulation of transcription factor targets across tumor types
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s13073-015-0260-1
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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