Gene

POLE

DNA polymerase epsilon, catalytic subunit

Explore in graph →CI-GENE-00020332HGNC:9177 ENSG00000177084 NCBI 5426 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (14)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–14 of 14 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
POLE L424I1
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	2	submitted

Cohorts

Alteration frequency by cohort (159)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved159 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Small-Cell Lung Cancer (Multi-Institute, Cancer Cell 2017) sclc_cancercell_gardner_2017	Lung Small Cell Carcinoma	Ssm

Literature

Linked publications (3)

25 per page, newest first.

pubmedPublishedShowing 1–3 of 3 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study.
· Lancet Gastroenterol Hepatol · 2016 · PMID 28404093 · validated civic_curation pubmed
Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy.
· Cancer Discov · 2016 · PMID 27683556 · validated civic_curation pubmed
Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer.
· J Clin Invest · 2016 · PMID 27159395 · validated civic_curation pubmed

POLE L424V1
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	5	submitted	EID10627 Functional evidence of mutator phenotype PMID 29352080 · Barbari et al., 2018 · Open in CIViC	civic

POLE L424V1

(functional)

—UNRESOLVED

Functional

Supports Loss Of Function

submitted

EID10627

Functional evidence of mutator phenotype

PMID 29352080 · Barbari et al., 2018 · Open in CIViC

civic

POLE Mutation3
Pembrolizumab	GlioblastomaCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	accepted	EID1861 Case report of a patient with glioblastoma multiforme and POLE germline mutation. The patient was treated with pembrolizumab and lymphocyte infiltration was noted after resection of a spinal metastasi… (full text at CIViC) PMID 27683556 · Johanns et al., 2016 · Open in CIViC	civic
〃	Malignant Endometrial NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	accepted	EID1862 Case report of a patient with endometrial cancer and exceptional response to pembrolizumab (maintained at 14 months). POLE mutations V411L (exonuclease domain) and R114* were identified in the primary… (full text at CIViC) PMID 27159395 · Mehnert et al., 2016 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	3	submitted	EID7469 In a case report, patient with metastatic colorectal cancer harboring MSS and POLE mutation was treated with pembrolizumab and showed tumor response. PMID 28188185 · Gong et al., 2017 · Open in CIViC	civic

POLE Mutation3

Pembrolizumab

GlioblastomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID1861

Case report of a patient with glioblastoma multiforme and POLE germline mutation. The patient was treated with pembrolizumab and lymphocyte infiltration was noted after resection of a spinal metastasi… (full text at CIViC)

PMID 27683556 · Johanns et al., 2016 · Open in CIViC

civic

〃

Malignant Endometrial NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID1862

Case report of a patient with endometrial cancer and exceptional response to pembrolizumab (maintained at 14 months). POLE mutations V411L (exonuclease domain) and R114* were identified in the primary… (full text at CIViC)

PMID 27159395 · Mehnert et al., 2016 · Open in CIViC

civic

〃

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID7469

In a case report, patient with metastatic colorectal cancer harboring MSS and POLE mutation was treated with pembrolizumab and showed tumor response.

PMID 28188185 · Gong et al., 2017 · Open in CIViC

civic

POLE P286H1
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	2	submitted	EID11041 POLE mutations observed in CRC or endometrial cancer were introduced by site-directed mutagenesis. Each mutation dramatically reduced 3′-5′ exonuclease activity relative to the wild-type POLE in in vi… (full text at CIViC) PMID 25228659 · Shinbrot et al., 2014 · Open in CIViC	civic

POLE P286H1

(functional)

—UNRESOLVED

Functional

Supports Loss Of Function

submitted

EID11041

POLE mutations observed in CRC or endometrial cancer were introduced by site-directed mutagenesis. Each mutation dramatically reduced 3′-5′ exonuclease activity relative to the wild-type POLE in in vi… (full text at CIViC)

PMID 25228659 · Shinbrot et al., 2014 · Open in CIViC

civic

POLE P286R2
(prognostic)	Malignant Endometrial NeoplasmCURATED_BROADER	Prognostic	A	Supports Better Outcome	5	submitted	EID13113 In the PORTEC-3 trial cohort, POLE-ultramutated (POLEmut) endometrial carcinomas had a 98% five-year recurrence-free survival, independent of the adjuvant treatment arm. Variant P286R is the most comm… (full text at CIViC) PMID 32749941 · León-Castillo et al., 2020 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Supports Better Outcome	3	accepted	EID5017 POLE proofreading domain mutations identify a subset of immunogenic colorectal cancers with excellent prognosis. PMID 28404093 · Domingo et al., 2016 · Open in CIViC	civic

POLE P286R2

(prognostic)

Malignant Endometrial NeoplasmCURATED_BROADER

Prognostic

Supports Better Outcome

submitted

EID13113

In the PORTEC-3 trial cohort, POLE-ultramutated (POLEmut) endometrial carcinomas had a 98% five-year recurrence-free survival, independent of the adjuvant treatment arm. Variant P286R is the most comm… (full text at CIViC)

PMID 32749941 · León-Castillo et al., 2020 · Open in CIViC

civic

〃

Malignant Colorectal NeoplasmCURATED_BROADER

Prognostic

Supports Better Outcome

accepted

EID5017

POLE proofreading domain mutations identify a subset of immunogenic colorectal cancers with excellent prognosis.

PMID 28404093 · Domingo et al., 2016 · Open in CIViC

civic

POLE R1233*2
(oncogenic)	High-Grade Glioma, NOS	Oncogenic	C	Does Not Support Oncogenicity	3	submitted	EID12524 A 14-year old patient with bi-allelic PMS2 pathogenic germline variants (c.2 T>A, p.M1K and c.2521del, p.W841Gfs*10) and a diagnosis of constitutional mismatch repair deficiency (CMMRD) was diagnosed … (full text at CIViC) PMID 38773265 · Palova et al., 2024 · Open in CIViC	civic
〃	Endometrial AdenocarcinomaCURATED_BROADER	Oncogenic	C	Does Not Support Oncogenicity	2	submitted	EID12525 Studies submitted to cBioPortal (including 164 TCGA studies) were evaluated for POLE variants co-occurring with features of POLE-mutated tumors and co-occurring B2M variants. A single individual with … (full text at CIViC) PMID 29320758 · Voutsadakis, 2018 · Open in CIViC	civic

POLE R1233*2

(oncogenic)

High-Grade Glioma, NOS

Oncogenic

Does Not Support Oncogenicity

submitted

EID12524

A 14-year old patient with bi-allelic PMS2 pathogenic germline variants (c.2 T>A, p.M1K and c.2521del, p.W841Gfs*10) and a diagnosis of constitutional mismatch repair deficiency (CMMRD) was diagnosed … (full text at CIViC)

PMID 38773265 · Palova et al., 2024 · Open in CIViC

civic

〃

Endometrial AdenocarcinomaCURATED_BROADER

Oncogenic

Does Not Support Oncogenicity

submitted

EID12525

Studies submitted to cBioPortal (including 164 TCGA studies) were evaluated for POLE variants co-occurring with features of POLE-mutated tumors and co-occurring B2M variants. A single individual with … (full text at CIViC)

PMID 29320758 · Voutsadakis, 2018 · Open in CIViC

civic

POLE S459F1
(prognostic)	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Supports Better Outcome	3	accepted	EID5019 POLE proofreading domain mutations identify a subset of immunogenic colorectal cancers with excellent prognosis. PMID 28404093 · Domingo et al., 2016 · Open in CIViC	civic

POLE S459F1

(prognostic)

Malignant Colorectal NeoplasmCURATED_BROADER

Prognostic

Supports Better Outcome

accepted

EID5019

POLE proofreading domain mutations identify a subset of immunogenic colorectal cancers with excellent prognosis.

PMID 28404093 · Domingo et al., 2016 · Open in CIViC

civic

POLE V411L3
(prognostic)	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Supports Better Outcome	3	accepted	EID5018 POLE proofreading domain mutations identify a subset of immunogenic colorectal cancers with excellent prognosis. PMID 28404093 · Domingo et al., 2016 · Open in CIViC	civic
Unspecified therapy	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	C	Supports Sensitivity Response	2	submitted	EID8631 "CRCs with POLE proofreading deficiency had characteristics distinct from those of other CRCs. Analysis of POLE proofreading deficiency may be clinically significant for personalized management of CRC… (full text at CIViC) PMID 31240875 · Hino et al., 2019 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	5	submitted	EID10626 Genetic and biochemical evidence for functional significance. PMID 35822874 · Barbari et al., 2022 · Open in CIViC	civic

POLE V411L3

(prognostic)

Malignant Colorectal NeoplasmCURATED_BROADER

Prognostic

Supports Better Outcome

accepted

EID5018

POLE proofreading domain mutations identify a subset of immunogenic colorectal cancers with excellent prognosis.

PMID 28404093 · Domingo et al., 2016 · Open in CIViC

civic

Unspecified therapy

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID8631

"CRCs with POLE proofreading deficiency had characteristics distinct from those of other CRCs. Analysis of POLE proofreading deficiency may be clinically significant for personalized management of CRC… (full text at CIViC)

PMID 31240875 · Hino et al., 2019 · Open in CIViC

civic

(functional)

—UNRESOLVED

Functional

Supports Loss Of Function

submitted

EID10626

Genetic and biochemical evidence for functional significance.

PMID 35822874 · Barbari et al., 2022 · Open in CIViC

civic