ArticleEuropean journal of human genetics : EJHG2011
Concurrent genetic alterations in DNA polymerase proofreading and mismatch repair in human colorectal cancer.
Article in European journal of human genetics : EJHG, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- From Molecular Classification to Hereditary Cancer Syndrome Identification in Endometrial Cancer.Genes · 2026Article
- Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variants.Life science alliance · 2024Review
- Review
- POLE/POLD1 mutation and tumor immunotherapy.Journal of experimental & clinical cancer research : CR · 2022Review
- Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.Annual review of biochemistry · 2022Review
- Review
- POLE2 facilitates the malignant phenotypes of glioblastoma through promoting AURKA-mediated stabilization of FOXM1.Cell death & disease · 2022Article
- Rate volatility and asymmetric segregation diversify mutation burden in cells with mutator alleles.Communications biology · 2021Article
- Complete Response to Pembrolizumab in Advanced Colon Cancer Harboring Somatic POLE F367S Mutation with Microsatellite Stability Status: A Case Study.OncoTargets and therapy · 2021Article
- Article
- POLE Mutation Spectra Are Shaped by the Mutant Allele Identity, Its Abundance, and Mismatch Repair Status.Molecular cell · 2020Article
- Regulation of the error-prone DNA polymerase Polκ by oncogenic signaling and its contribution to drug resistance.Science signaling · 2020Article
- Article
- POLE proofreading defects: Contributions to mutagenesis and cancer.DNA repair · 2019Review
- Risk of colorectal cancer for carriers of a germ-line mutation in POLE or POLD1.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Article
- Functional Analysis of Cancer-Associated DNA Polymerase ε Variants inG3 (Bethesda, Md.) · 2018Article
- Family A and B DNA Polymerases in Cancer: Opportunities for Therapeutic Interventions.Biology · 2018Review
- Nucleotide selectivity defect and mutator phenotype conferred by a colon cancer-associated DNA polymerase δ mutation in human cells.Oncogene · 2017Article
- Replicative DNA polymerase defects in human cancers: Consequences, mechanisms, and implications for therapy.DNA repair · 2017Review
- DNA Polymerase ɛ Deficiency Leading to an Ultramutator Phenotype: A Novel Clinically Relevant Entity.The oncologist · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genomic sequences encoding the 3' exonuclease (proofreading) domains of both replicative DNA polymerases, pol delta and pol epsilon, were explored simultaneously in human colorectal carcinomas including six established cell lines. Three unequivocal sequence alterations, including one previously reported, were found, and all these were considered as dysfunctional mutations in light of the local amino-acid sequences. In particular, the F367S mutation found in the POLE gene encoding the pol epsilon catalytic subunit, which includes the proofreading domain, is the first found in human diseases. Surprisingly, the tumours carrying these proofreading domain mutations were all defective in DNA mismatch repair (MMR). In addition to the two cell lines with acknowledged MMR gene mutations, the third tumour was also demonstrated to harbour a distinct mutation in MLH1, and indeed exhibited a microsatellite-unstable phenotype. These findings suggest that, in concert with MMR deficiency, defective polymerase proofreading may also contribute to the mutator phenotype observed in human colorectal cancer. Our observations may suggest previously unrecognised complexities in the molecular abnormalities underlying the mutator phenotype in human neoplasms.
Indexed as
Identifiers
What OpenQuestion holds
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.