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

Genome Medicine
Abel Gonzalez-Perez

Abstract

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. 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. I 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 identif...Continue Reading

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Methods Mentioned

BETA
RNAseq
ChIP-seq
ubiquitination

Software Mentioned

MSigDB
TRANSFAC
Gitools
PathwayCommons2
pazar
ENCODE
InterPro
IntOGen
SLEA

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