Mutational processes in cancer preferentially affect binding of particular transcription factors.
Abstract
Protein binding microarrays provide comprehensive information about the DNA binding
specificities of transcription factors (TFs), and can be used to quantitatively predict
the effects of DNA sequence variation on TF binding. There has also been substantial
progress in dissecting the patterns of mutations, i.e., the "mutational signatures",
generated by different mutational processes. By combining these two layers of information
we can investigate whether certain mutational processes tend to preferentially affect
binding of particular classes of TFs. Such preferential alterations of binding might
predispose to particular oncogenic pathways. We developed and implemented a method,
termed "Signature-QBiC", that integrates protein binding microarray data with the
signatures of mutational processes, with the aim of predicting which TFs' binding
profiles are preferentially perturbed by particular mutational processes. We used
Signature-QBiC to predict the effects of 47 signatures of mutational processes on
582 human TFs. Pathway analysis showed that binding of TFs involved in NOTCH1 signaling
is strongly affected by the signatures of several mutational processes, including
exposure to ultraviolet radiation. Additionally, toll-like-receptor signaling pathways
are also vulnerable to disruption by this exposure. This study provides a novel overview
of the effects of mutational processes on TF binding and the potential of these processes
to activate oncogenic pathways through mutating TF binding sites.
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Journal articlePermalink
https://hdl.handle.net/10161/22413Published Version (Please cite this version)
10.1038/s41598-021-82910-0Publication Info
Liu, Mo; Boot, Arnoud; Ng, Alvin WT; Gordân, Raluca; & Rozen, Steven G (2021). Mutational processes in cancer preferentially affect binding of particular transcription
factors. Scientific reports, 11(1). pp. 3339. 10.1038/s41598-021-82910-0. Retrieved from https://hdl.handle.net/10161/22413.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Steven George Rozen
Associate Professor in Psychiatry and Behavioral Sciences

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