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POLE (DNA polymerase epsilon catalytic subunit A) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Ovarian cancer, Lung cancer and 5 more.
Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication. Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork.
CIViC holds 14 clinical evidence items and 0 assertions across 8 variants, naming Pembrolizumab. Open Targets scores its association with cancer at 0.88 (direct and indirect evidence; datatypes genetic literature 0.78, clinical 0.99, affected pathway 0.76, literature 0.98, genetic association 0.82, somatic mutation 0.80). IntOGen calls it a driver in 2 cohorts (2 activating, 0 loss-of-function), covering Adrenocortical Carcinoma, Bladder Urothelial Carcinoma.
In plain words · POLE (DNA polymerase epsilon catalytic subunit A) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Ovarian cancer, Lung cancer and 5 more.
POLE (DNA polymerase epsilon catalytic subunit A) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a biomarker and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Ovarian cancer, Lung cancer and 5 more.
Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication.
No product in this corpus aims at POLE yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance); what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA POLE: RNA tissue enhanced (bone marrow 21 nTPM); no normal tissue stained high. Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Ovarian cancer, Lung cancer (all types), Breast cancer (all types), Lymphoma, Leukaemia, Myeloid neoplasms and more); Open Targets associates it with 16 specific cancer types at or above 0.5 (colorectal cancer, susceptibility to, 12, non-small cell lung carcinoma, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, exocrine pancreatic carcinoma, acute lymphoblastic leukemia and more). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt Q07864; CIViC gene POLE; IntOGen POLE; Human Protein Atlas POLE tissue; Open Targets ENSG00000177084 associations
First described 1993. Earliest sequence paper UniProt cites for the protein: Kesti et al, J. Biol. Chem, 1993, "Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase epsilon". Source.
Sources: HGNC HGNC:9177 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q07864 (protein name, function text, keywords and locations (REST API)); CIViC gene POLE (14 evidence items, 0 assertions, 8 variants; diseases: Colorectal Cancer, Endometrial Cancer, Glioblastoma, Endometrial Adenocarcinoma, High Grade Glioma (GraphQL API, CC0)); Open Targets ENSG00000177084 (association with cancer (MONDO_0004992) 0.88; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.70, colorectal cancer 0.77, gastric cancer 0.53, urinary bladder cancer 0.52, ovarian cancer 0.75, endometrial cancer 0.62 (GraphQL API, CC0)); IntOGen POLE (driver in 2 cohorts (Act 2, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Catalytic component of the DNA polymerase epsilon complex. Participates in chromosomal DNA replication. Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork. Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication. Involved in DNA synthesis during DNA repair. Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation. Location: Nucleus (UniProt). Locus 12q24.33 (HGNC).
RNA: tissue enhanced (bone marrow 21 nTPM), detected in many normal tissues.
No normal tissue stained high.
No cancer sample stained medium or high.
HPA POLE tissue · HPA POLE pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Colorectal cancer | 0.7-2% | Exonuclease (proofreading) domain hotspot mutation, ultramutated tumours | Pathogenic somatic POLE mutations in 66 of 6,517 colorectal cancers, 1.0%, across nine trials and cohorts (Domingo 2016). cBioPortal, counting only exonuclease hotspots (P286R, V411L, S297F, S459F and their neighbours): 52 of 7,237, 0.7%, in crc_msk_2026; 8 of 1,134 in crc_msk_2017; 11 of 534, 2.1%, in coadread_tcga_pan_can_atlas_2018; 6 of 224 in coadread_tcga_pub; 5 of 619 in coadread_dfci_2016; 12 of 1,015 in crc_sysucc_2022. The studies' own molecular subtype attributes agree: POLE in 8 of 1,134 (crc_msk_2017) and 13 of 1,468 (crc_eo_2020). | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It defines a small group with an excellent prognosis that no repair immunohistochemistry panel or MSI assay will find, and it is the main argument for sequencing rather than staining alone in younger patients.
POLE and POLD1 are now on polyposis and colorectal germline panels, and the paper explains why a patient with many adenomas and an entirely normal mismatch repair panel still needs sequencing.
Query for this target: (TITLE:"POLE" OR ABSTRACT:"POLE" OR TITLE:"DNA polymerase epsilon, catalytic subunit" OR ABSTRACT:"DNA polymerase epsilon, catalytic subunit" OR TITLE:"DNA polymerase epsilon catalytic subunit A" OR ABSTRACT:"DNA polymerase epsilon catalytic subunit A" OR TITLE:"POLE1" OR ABSTRACT:"POLE1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about POLE, not a curated reading list.
Shares Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas, POLE ultramutation (POLEmut), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types).
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), CIViC, IntOGen.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), CIViC, Ovarian cancer.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), Endometrial cancer, CIViC.
Shares Leukaemia (all types), Endometrial cancer, CIViC, IntOGen.
Shares Myeloproliferative neoplasms (PV, ET, myelofibrosis), Leukaemia (all types), CIViC, IntOGen.
Shares Leukaemia (all types), Endometrial cancer, CIViC, IntOGen.
Shares Leukaemia (all types), CIViC, IntOGen, Lung cancer (all types).