ArticleClinical epigenetics2021
Clinical and epigenetic features of colorectal cancer patients with somatic POLE proofreading mutations.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Mutation enrichment in targeted panels flags immunotherapy-responsive POLE-driven hypermutated microsatellite-stable colorectal cancers.NPJ precision oncology · 2026Article
- Review
- Emerging role of DNA polymerase epsilon non-exonuclease domain mutations in colorectal cancer: From sequence variants to clinical implications.World journal of gastroenterology · 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
- Whole-Exome Sequencing Analysis of Inflammatory Bowel Disease-Associated Serrated Dysplasia.International journal of molecular sciences · 2025Article
- Clinicopathologic Analysis of Five Patients withDiagnostics (Basel, Switzerland) · 2025Article
- Predictors of response to immunotherapy in colorectal cancer.The oncologist · 2024Review
- Deep learning for dual detection of microsatellite instability and POLE mutations in colorectal cancer histopathology.NPJ precision oncology · 2024Article
- The game-changing impact ofFrontiers in oncology · 2024Review
- Histomorphological and molecular genetic characterization of different intratumoral regions and matched metastatic lymph nodes of colorectal cancer with heterogenous mismatch repair protein expression.Journal of cancer research and clinical oncology · 2023Article
- Article
- Reprogrammed Lipid Metabolism and the Lipid-Associated Hallmarks of Colorectal Cancer.Cancers · 2022Review
- Distinct clinical pattern of colorectal cancer patients with POLE mutations: A retrospective study on real-world data.Frontiers in genetics · 2022Article
- Prognostic significance of Notch3 immunoreactivity patterns in Caucasian colon adenocarcinoma patients.Przeglad gastroenterologiczny · 2022Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundMutations in the POLE gene result in an ultra-hypermutated phenotype in colorectal cancer (CRC); however, the molecular characterisation of epigenetic alterations remains unclear. We examined the genetic and epigenetic profiles of POLE-mutant CRC to elucidate the clinicopathological features of the associated genetic and epigenetic alterations.
resultsTumour tissues (1,013) obtained from a cohort of patients with CRC were analysed to determine associations between the proofreading domain mutations of POLE with various clinicopathological variables, microsatellite instability (MSI) status, BRAF and KRAS mutations, and the methylation status of key regions of MLH1, MGMT, and SFRP2 promoters by calculating the methylation scores (range 0-6). Only four cases (0.4%) exhibited pathogenic POLE hotspot mutations (two p.P286R [c.857C > G], one p.V411L [c.1231G > C], and p.S459F [c.1376C > T] each), which were mutually exclusive to BRAF and KRAS mutations and MSI. CRC patients were divided into four subgroups: patients with POLE mutations (POLE, 0.4%, n = 4), patients with both MSI and extensive methylation in MLH1 (MSI-M, 2.9%, n = 29), patients with MSI but no extensive methylation in MLH1 (MSI-U, 3.6%, n = 36), and patients without MSI (non-MSI, 93.2%, n = 944). The POLE group was younger at diagnosis (median 52 years, P < 0.0001), with frequent right-sided tumour localisation (frequency of tumours located in the right colon was 100%, 93.1%, 36.1%, and 29.9% in POLE, MSI-M, MSI-U, and non-MSI, respectively; P < 0.0001), and was diagnosed at an earlier stage (frequency of stages I-II was 100%, 72.4%, 77.8%, and 46.6% in POLE, MSI-M, MSI-U, and non-MSI, respectively, P < 0.0001). The mean methylation score in POLE was not different from that in MSI-U and non-MSI, but the methylation signature was distinct from that of the other subgroups. Additionally, although the examined number of POLE-mutant tumours was small, the number of CD8-positive cells increased in tumours with partial methylation in the MLH1 gene.
conclusionsCRC patients with POLE proofreading mutations are rare. Such mutations are observed in younger individuals, and tumours are primarily located in the right colon. Diagnosis occurs at an earlier stage, and distinct epigenetic alterations may be associated with CD8 cell infiltration.
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