ArticleBMC genomics2016
Negative selection maintains transcription factor binding motifs in human cancer.
Article in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- HOCOMOCO in 2024: a rebuild of the curated collection of binding models for human and mouse transcription factors.Nucleic acids research · 2024Article
- The Causes for Genomic Instability and How to Try and Reduce Them Through Rational Design of Synthetic DNA.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of gene regulatory programs in cancers.Nucleic acids research · 2022Article
- GRAFIMO: Variant and haplotype aware motif scanning on pangenome graphs.PLoS computational biology · 2021Article
- Functional annotation of noncoding mutations in cancer.Life science alliance · 2021Article
- Prediction of genome-wide effects of single nucleotide variants on transcription factor binding.Scientific reports · 2020Article
- Interplay between whole-genome doubling and the accumulation of deleterious alterations in cancer evolution.Nature genetics · 2020Article
- CpG traffic lights are markers of regulatory regions in human genome.BMC genomics · 2019Article
- DNA Motif Recognition Modeling from Protein Sequences.iScience · 2018Article
- Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.Genome biology · 2018Article
- HOCOMOCO: towards a complete collection of transcription factor binding models for human and mouse via large-scale ChIP-Seq analysis.Nucleic acids research · 2018Article
- Overexpressed somatic alleles are enriched in functional elements in Breast Cancer.Scientific reports · 2017Article
- VarI-SIG 2015: methods for personalized medicine - the role of variant interpretation in research and diagnostics.BMC genomics · 2016Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSomatic mutations in cancer cells affect various genomic elements disrupting important cell functions. In particular, mutations in DNA binding sites recognized by transcription factors can alter regulator binding affinities and, consequently, expression of target genes. A number of promoter mutations have been linked with an increased risk of cancer. Cancer somatic mutations in binding sites of selected transcription factors have been found under positive selection. However, action and significance of negative selection in non-coding regions remain controversial.
resultsHere we present analysis of transcription factor binding motifs co-localized with non-coding variants. To avoid statistical bias we account for mutation signatures of different cancer types. For many transcription factors, including multiple members of FOX, HOX, and NR families, we show that human cancers accumulate fewer mutations than expected by chance that increase or decrease affinity of predicted binding sites. Such stability of binding motifs is even more exhibited in DNase accessible regions.
conclusionsOur data demonstrate negative selection against binding sites alterations and suggest that such selection pressure protects cancer cells from rewiring of regulatory circuits. Further analysis of transcription factors with conserved binding motifs can reveal cell regulatory pathways crucial for the survivability of various human cancers.
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