ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
Role of POLE and POLD1 in familial cancer.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2024 for the clinical practice of hereditary colorectal cancer.International journal of clinical oncology · 2026Guideline
- Optimizing GRIDSS for clinical use: A targeted NGS filtering strategy for germline structural variant detection.European journal of human genetics : EJHG · 2026Article
- Idylla™ POLE-POLD1 mutation assay for molecular characterization and risk stratification of endometrial cancers: a retrospective multicenter validation study.Virchows Archiv : an international journal of pathology · 2026Article
- Interpreting the effects of DNA polymerase variants at the structural level.Molecular oncology · 2026Article
- Prognostic, Predictive, and Clinical Relevance of DNA Damage Repair Alterations in Biliary Tract Cancers.Cancers · 2026Review
- Review
- Decoding Immunotherapy Response in Colorectal Cancer: Translational Insights Beyond MSI.Cancers · 2026Review
- Functional Characterization ofDiseases (Basel, Switzerland) · 2026Article
- Rare Germline Variants in CDKN2A-Negative Children and Adolescents With Cutaneous Melanoma.Pigment cell & melanoma research · 2026Article
- Hereditary cancer syndromes with gynecological cancer risk: focus on prevention strategies.Frontiers in oncology · 2026Review
- Inborn errors of immunity with DNA repair disorders: at the interface of immune deficiency, immune dysregulation, and malignancy.Frontiers in immunology · 2026Review
- Whole-exome sequencing for identification of specific gene mutations in an Indian cohort of triple-negative breast cancer patients.Discover oncology · 2025Article
- Advances in Hereditary Colorectal Cancer: How Precision Medicine Is Changing the Game.Cancers · 2025Review
- Endometrial cancer: from clinical reality to molecular treatment.Discover oncology · 2025Review
- POLE Deficiency Exacerbates Diesel Engine Exhaust-Induced Genomic Instability and Malignant Transformation of Bronchial Epithelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Genetic predisposition to polyposis syndromes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Upregulation of POLE and proficient DNA repair are features of CIC::DUX4 sarcomas.NPJ precision oncology · 2025Article
- Mutational Patterns in Colorectal Cancer: Do PDX Models Retain the Heterogeneity of the Original Tumor?International journal of molecular sciences · 2025Article
- PolED: a manually curated database of functional studies of POLE and POLD1 variants reported in humans.Database : the journal of biological databases and curation · 2025Article
- Carcinogenesis trajectories.Frontiers in cell and developmental biology · 2025Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGermline pathogenic variants in the exonuclease domain (ED) of polymerases POLE and POLD1 predispose to adenomatous polyps, colorectal cancer (CRC), endometrial tumors, and other malignancies, and exhibit increased mutation rate and highly specific associated mutational signatures. The tumor spectrum and prevalence of POLE and POLD1 variants in hereditary cancer are evaluated in this study.
methodsPOLE and POLD1 were sequenced in 2813 unrelated probands referred for genetic counseling (2309 hereditary cancer patients subjected to a multigene panel, and 504 patients selected based on phenotypic characteristics). Cosegregation and case-control studies, yeast-based functional assays, and tumor mutational analyses were performed for variant interpretation.
resultsTwelve ED missense variants, 6 loss-of-function, and 23 outside-ED predicted-deleterious missense variants, all with population allele frequencies <1%, were identified. One ED variant (POLE p.Met294Arg) was classified as likely pathogenic, four as likely benign, and seven as variants of unknown significance. The most commonly associated tumor types were colorectal, endometrial and ovarian cancers. Loss-of-function and outside-ED variants are likely not pathogenic for this syndrome.
conclusionsPolymerase proofreading-associated syndrome constitutes 0.1-0.4% of familial cancer cases, reaching 0.3-0.7% when only CRC and polyposis are considered. ED variant interpretation is challenging and should include multiple pieces of evidence.
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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.