ArticleFamilial cancer2015
A novel POLE mutation associated with cancers of colon, pancreas, ovaries and small intestine.
Article in Familial cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01904630 (Exom-sekvensering for å Identifisere høyrisiko Genvarianter i en Familie Predisponert for Colorectal Cancer), which is not on this map. Cited by 55 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.
Exom-sekvensering for å Identifisere høyrisiko Genvarianter i en Familie Predisponert for Colorectal Cancer
Who cites it
55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 84 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
- Cancer Predisposition Genes in Adolescents and Young Adults (AYAs): a Review Paper from the Italian AYA Working Group.Current oncology reports · 2022Pooled it
- A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
- 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
- Exome sequencing reveals new insights into the germline landscape of inflammatory breast cancer among Tunisian patients.Journal of translational medicine · 2025Article
- Comprehensive Analysis of Human Colorectal Cancers Harboring Polymerase Epsilon Mutations.International journal of molecular sciences · 2025Article
- Prevalence of germline variants in Brazilian pancreatic carcinoma patients.Scientific reports · 2024Article
- POLE-Mutant Colon Adenocarcinoma-Case Presentation and Histopathological Evaluation.Journal of gastrointestinal cancer · 2024Article
- Molecular diagnostics of hepatobiliary and pancreatic neoplasias.Virchows Archiv : an international journal of pathology · 2024Review
- Article
- Article
- Characterization of POLE c.1373A > T p.(Tyr458Phe), causing high cancer risk.Molecular genetics and genomics : MGG · 2023Article
- Genetic Predisposition to Colorectal Cancer: How Many and Which Genes to Test?International journal of molecular sciences · 2023Review
- Whole genome sequencing identifies rare genetic variants in familial pancreatic cancer patients.Annals of human genetics · 2022Article
- The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management.Familial cancer · 2022Article
- Probing the mechanisms of two exonuclease domain mutators of DNA polymerase ϵ.Nucleic acids research · 2022Article
- The Roles of EXO1 and RPA1 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.Disease markers · 2022Article
- Review
- POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes.Oncogene · 2021Review
- Additive effects of variants of unknown significance in replication repair-associated DNA polymerase genes on mutational burden and prognosis across diverse cancers.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In some families there is an increased risk for colorectal cancer, caused by heritable, but often unidentified genetic mutations predisposing to the disease. We have identified the likely genetic cause for disease predisposition in a large family with high burden of colorectal adenomas and carcinomas, in addition to extra-colonic cancers. This family had previously been tested for known cancer susceptibility genes, with negative results. Exome sequencing was used to identify a novel mutation, c.1373A>T (p.Tyr458Phe), in the gene for DNA polymerase epsilon catalytic subunit (POLE). This mutation is located in the active site of the exonuclease domain of the enzyme, and affects a residue that has previously been shown to be important for exonuclease activity. The first predisposing mutation identified in POLE (c.1270C>G, p.Leu424Val) was associated with colorectal cancer only, but another mutation with a broader tumour spectrum (c.1089C>A, p.Asn363Lys) has recently been reported. In the family described in the present study, carriers generally have multiple colorectal adenomas and cancer of colon, pancreas, ovaries and small intestine which represents an important broadening of the tumour spectrum of POLE mutation carriers. We also observe a large phenotypic variation among the POLE mutation carriers in this family, most likely explained by modifying variants in other genes. One POLE mutation carrier has a novel variant in EXO1 (c.458C>T, p.Ala153Val), which may contribute to a more severe phenotype. The findings in this study will have important implications for risk assessment and surveillance of POLE mutation carriers.
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