ArticlePLoS genetics2020
Mutational processes of distinct POLE exonuclease domain mutants drive an enrichment of a specific TP53 mutation in colorectal cancer.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Ultra-mutated colorectal cancer patients with POLE driver mutations exhibit distinct clinical patterns.Cancer medicine · 2021Pooled it
- Emerging role of DNA polymerase epsilon non-exonuclease domain mutations in colorectal cancer: From sequence variants to clinical implications.World journal of gastroenterology · 2026Article
- Patterns of hypermutation shape tumorigenesis and immunotherapy response in mismatch-repair-deficient glioma.Nature genetics · 2026Article
- DNA polymerase epsilon-mutant colorectal cancers: Insights into non-exonuclease domain mutation variants, microsatellite instability status, and co-mutation profiles.World journal of gastroenterology · 2025Article
- Replication-associated mechanisms contribute to an increased CpG > TpG mutation burden in mismatch repair-deficient cancers.Genome medicine · 2025Article
- Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations.International journal of molecular sciences · 2025Article
- Genomic Differences and Distinct TP53 Mutation Site-Linked Chemosensitivity in Early- and Late-Onset Gastric Cancer.Cancer medicine · 2025Article
- Biomarkers and immunotherapy in endometrial cancer: mechanisms and clinical applications.Frontiers in immunology · 2025Review
- The Clinical and Pathological Characteristics of POLE-Mutated Endometrial Cancer: A Comprehensive Review.Cancer management and research · 2024Review
- The game-changing impact ofFrontiers in oncology · 2024Review
- A simple bypass assay for DNA polymerases shows that cancer-associated hypermutating variants exhibit differences in vitro.The FEBS journal · 2023Article
- Sequence dependencies and mutation rates of localized mutational processes in cancer.Genome medicine · 2023Article
- Cancer driver mutations: predictions and reality.Trends in molecular medicine · 2023Review
- Article
- Review
- Mouse model and human patient data reveal critical roles for Pten and p53 in suppressing POLE mutant tumor development.NAR cancer · 2022Article
- Clinical and Molecular Characterization ofJCO precision oncology · 2022Article
- Deficiency of replication-independent DNA mismatch repair drives a 5-methylcytosine deamination mutational signature in cancer.Science advances · 2021Article
- The origin of human mutation in light of genomic data.Nature reviews. Genetics · 2021Review
- A data-driven approach for constructing mutation categories for mutational signature analysis.PLoS computational biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer genomes with mutations in the exonuclease domain of Polymerase Epsilon (POLE) present with an extraordinarily high somatic mutation burden. In vitro studies have shown that distinct POLE mutants exhibit different polymerase activity. Yet, genome-wide mutation patterns and driver mutation formation arising from different POLE mutants remains unclear. Here, we curated somatic mutation calls from 7,345 colorectal cancer samples from published studies and publicly available databases. These include 44 POLE mutant samples including 9 with whole genome sequencing data available. The POLE mutant samples were categorized based on the specific POLE mutation present. Mutation spectrum, associations of somatic mutations with epigenomics features and co-occurrence with specific driver mutations were examined across different POLE mutants. We found that different POLE mutants exhibit distinct mutation spectrum with significantly higher relative frequency of C>T mutations in POLE V411L mutants. Our analysis showed that this increase frequency in C>T mutations is not dependent on DNA methylation and not associated with other genomic features and is thus specifically due to DNA sequence context alone. Notably, we found strong association of the TP53 R213* mutation specifically with POLE P286R mutants. This truncation mutation occurs within the TT[C>T]GA context. For C>T mutations, this sequence context is significantly more likely to be mutated in POLE P286R mutants compared with other POLE exonuclease domain mutants. This study refines our understanding of DNA polymerase fidelity and underscores genome-wide mutation spectrum and specific cancer driver mutation formation observed in POLE mutant cancers.
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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.