ArticlePLoS computational biology2018
Two critical positions in zinc finger domains are heavily mutated in three human cancer types.
Article in PLoS computational biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- A comprehensive meta-analysis of transcriptome data to identify signature genes associated with pancreatic ductal adenocarcinoma.PloS one · 2024Pooled it
- Dissecting cancer in a non-mammalian model: genomic insights from lemon frost geckos.BMC biology · 2026Article
- Proteasomal control of transcription factors: mechanisms, regulation and dysregulation.Cellular and molecular life sciences : CMLS · 2026Review
- Synchronous rectal and endometrial cancer: A case report and literature review.Oncology letters · 2026Article
- Integrative Meta-Analysis and WGCNA Reveal Candidate Diagnostic Hub Genes in Clear Cell Carcinoma.International journal of cell biology · 2026Article
- Genomic and Transcriptomic Landscapes of MEN1-Wild-Type Low-Grade Metastatic Pancreatic NETs Uncover Key Oncogenic Drivers and Targetable Pathways.International journal of biological sciences · 2026Article
- Review Article on Molecular Basis of Zinc and Copper Interactions in Cancer Physiology.Biological trace element research · 2025Review
- Formerly degenerate seventh zinc finger domain from transcription factor ZNF711 rehabilitated by experimental NMR structure.Protein science : a publication of the Protein Society · 2024Article
- Machine learning and multi-omics data reveal driver gene-based molecular subtypes in hepatocellular carcinoma for precision treatment.PLoS computational biology · 2024Article
- Formerly degenerate seventh zinc finger domain from transcription factor ZNF711 rehabilitated by experimental NMR structure.bioRxiv : the preprint server for biology · 2024Article
- Article
- Z-flipon variants reveal the many roles of Z-DNA and Z-RNA in health and disease.Life science alliance · 2023Article
- The Roles of Zinc Finger Proteins in Colorectal Cancer.International journal of molecular sciences · 2023Review
- Epitope Fine Mapping by Mass Spectrometry: Investigations of Immune Complexes Consisting of Monoclonal Anti-HpTGEKP Antibody and Zinc Finger Protein Linker Phospho-Hexapeptides.Chembiochem : a European journal of chemical biology · 2022Article
- Familial Predisposition to Leiomyomata: Searching for Protective Genetic Factors.Biomedicines · 2022Article
- The Identification of Zinc-Finger Protein 433 as a Possible Prognostic Biomarker for Clear-Cell Renal Cell Carcinoma.Biomolecules · 2021Article
- Recurrent ZNF83-E293V Mutation Promotes Bladder Cancer Progression through the NF-κB Pathway via Transcriptional Dysregulation of S100A8.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Signatures of Discriminative Copy Number Aberrations in 31 Cancer Subtypes.Frontiers in genetics · 2021Article
- The Role of Zinc and Copper in Gynecological Malignancies.Nutrients · 2020Review
- Cancer and pH Dynamics: Transcriptional Regulation, Proteostasis, and the Need for New Molecular Tools.Cancers · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A major goal of cancer genomics is to identify somatic mutations that play a role in tumor initiation or progression. Somatic mutations within transcription factors are of particular interest, as gene expression dysregulation is widespread in cancers. The substantial gene expression variation evident across tumors suggests that numerous regulatory factors are likely to be involved and that somatic mutations within them may not occur at high frequencies across patient cohorts, thereby complicating efforts to uncover which ones are cancer-relevant. Here we analyze somatic mutations within the largest family of human transcription factors, namely those that bind DNA via Cys2His2 zinc finger domains. Specifically, to hone in on important mutations within these genes, we aggregated somatic mutations across all of them by their positions within Cys2His2 zinc finger domains. Remarkably, we found that for three classes of cancers profiled by The Cancer Genome Atlas (TCGA)-Uterine Corpus Endometrial Carcinoma, Colon and Rectal Adenocarcinomas, and Skin Cutaneous Melanoma-two specific, functionally important positions within zinc finger domains are mutated significantly more often than expected by chance, with alterations in 18%, 10% and 43% of tumors, respectively. Numerous zinc finger genes are affected, with those containing Krüppel-associated box (KRAB) repressor domains preferentially targeted by these mutations. Further, the genes with these mutations also have high overall missense mutation rates, are expressed at levels comparable to those of known cancer genes, and together have biological process annotations that are consistent with roles in cancers. Altogether, we introduce evidence broadly implicating mutations within a diverse set of zinc finger proteins as relevant for cancer, and propose that they contribute to the widespread transcriptional dysregulation observed in cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.