ArticleEuropean journal of human genetics : EJHG2015
Germline variants in POLE are associated with early onset mismatch repair deficient colorectal cancer.
Article in European journal of human genetics : EJHG, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 124 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
- Guideline
- POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Pooled it
- ATM immunohistochemistry as an effective screening method for POLE variants among endometrial carcinomas lacking mismatch repair deficiency and p53 abnormalities.The journal of pathology. Clinical research · 2026Article
- Hereditary Endometrial Cancer: Lynch Syndrome, Mismatch Repair Deficiency, and Emerging Genetic Predispositions-A Comprehensive Review with Clinical and Laboratory Guidelines.International journal of molecular sciences · 2026Review
- Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations.International journal of molecular sciences · 2025Article
- Genetics, genomics and clinical features of adenomatous polyposis.Familial cancer · 2025Review
- Review
- POLD3 haploinsufficiency is linked to non-syndromic sensorineural adult-onset progressive hearing and balance impairments.European journal of human genetics : EJHG · 2025Article
- Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation.Cancer medicine · 2024Article
- Article
- Article
- Characterization of POLE c.1373A > T p.(Tyr458Phe), causing high cancer risk.Molecular genetics and genomics : MGG · 2023Article
- A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome.Journal of translational medicine · 2023Article
- A tumor focused approach to resolving the etiology of DNA mismatch repair deficient tumors classified as suspected Lynch syndrome.medRxiv : the preprint server for health sciences · 2023Article
- Unraveling the impact of a germline heterozygousFrontiers in molecular biosciences · 2023Article
- Whole-Exome Sequencing Identifies Pathogenic Germline Variants in Patients with Lynch-Like Syndrome.Cancers · 2022Article
- POLE/POLD1 mutation and tumor immunotherapy.Journal of experimental & clinical cancer research : CR · 2022Review
- The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management.Familial cancer · 2022Article
- Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Germline variants affecting the exonuclease domains of POLE and POLD1 predispose to multiple colorectal adenomas and/or colorectal cancer (CRC). The aim of this study was to estimate the prevalence of previously described heterozygous germline variants POLE c.1270C>G, p.(Leu424Val) and POLD1 c.1433G>A, p.(Ser478Asn) in a Dutch series of unexplained familial, early onset CRC and polyposis index cases. We examined 1188 familial CRC and polyposis index patients for POLE p.(Leu424Val) and POLD1 p.(Ser478Asn) variants using competitive allele-specific PCR. In addition, protein expression of the POLE and DNA mismatch repair genes was studied by immunohistochemistry in tumours from POLE carriers. Somatic mutations were screened using semiconductor sequencing. We detected three index patients (0.25%) with a POLE p.(Leu424Val) variant. In one patient, the variant was found to be de-novo. Tumours from three patients from two families were microsatellite instable, and immunohistochemistry showed MSH6/MSH2 deficiency suggestive of Lynch syndrome. Somatic mutations but no germline MSH6 and MSH2 variants were subsequently found, and one tumour displayed a hypermutator phenotype. None of the 1188 patients carried the POLD1 p.(Ser478Asn) variant. POLE germline variant carriers are also associated with a microsatellite instable CRC. POLE DNA analysis now seems warranted in microsatellite instable CRC, especially in the absence of a causative DNA mismatch repair gene germline variant.
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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.