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POLE Exonuclease Domain Mutation

MedGen UID:
1381761
•Concept ID:
C4330920
•
Cell or Molecular Dysfunction
Synonyms: DNA Polymerase Epsilon Catalytic Subunit A Exonuclease Domain Mutation; DNA Polymerase Epsilon, Catalytic Subunit Exonuclease Domain Mutation; POLE1 Exonuclease Domain Mutation

Definition

A missense mutation in the POLE gene located in the region that encodes the exonuclease domain of the DNA polymerase epsilon catalytic subunit A protein (POLE protein). These mutations lead to defective DNA proof-reading by POLE protein during DNA replication and have been reported in patients with colorectal carcinoma and certain subtypes of endometrial carcinoma. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • POLE Exonuclease Domain Mutation

Professional guidelines

PubMed

Potential of molecular classification to guide fertility-sparing management among young patients with endometrial cancer.
Agusti N, Kanbergs A, Nitecki R
Gynecol Oncol 2024 Jun;185:121-127. Epub 2024 Feb 24 doi: 10.1016/j.ygyno.2024.02.020. PMID: 38402734Free PMC Article
Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies.
Yang Y, Wu SF, Bao W
Int J Gynaecol Obstet 2024 Feb;164(2):436-459. Epub 2023 Jul 31 doi: 10.1002/ijgo.14969. PMID: 37525501
The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management.
Palles C, Martin L, Domingo E, Chegwidden L, McGuire J, Cuthill V, Heitzer E; CORGI Consortium, Kerr R, Kerr D, Kearsey S, Clark SK, Tomlinson I, Latchford A
Fam Cancer 2022 Apr;21(2):197-209. Epub 2021 May 5 doi: 10.1007/s10689-021-00256-y. PMID: 33948826Free PMC Article

Recent clinical studies

Etiology

Pathological complete response to immune checkpoint inhibitor in patients with colorectal cancer liver metastases harboring POLE exonuclease domain mutation.
Wen L, Chen Z, Ji X, Fong WP, Shao Q, Ren C, Cai Y, Li B, Yuan Y, Wang D, Li Y
J Immunother Cancer 2022 Jul;10(7) doi: 10.1136/jitc-2022-004487. PMID: 35793867Free PMC Article
Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma.
Kobayashi Kato M, Asami Y, Takayanagi D, Matsuda M, Shimada Y, Hiranuma K, Kuno I, Komatsu M, Hamamoto R, Matsumoto K, Ishikawa M, Kohno T, Kato T, Shiraishi K, Yoshida H
Cancer Sci 2022 May;113(5):1712-1721. Epub 2022 Mar 24 doi: 10.1111/cas.15328. PMID: 35278272Free PMC Article
Molecular characterization in the prediction of disease extent in endometrial carcinoma.
Kolehmainen AM, Pasanen AM, Koivisto-Korander RL, Bützow RC, Loukovaara MJ
Eur J Obstet Gynecol Reprod Biol 2021 Jan;256:478-483. Epub 2020 Oct 16 doi: 10.1016/j.ejogrb.2020.10.031. PMID: 33189427
Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations.
Hussein YR, Weigelt B, Levine DA, Schoolmeester JK, Dao LN, Balzer BL, Liles G, Karlan B, Köbel M, Lee CH, Soslow RA
Mod Pathol 2015 Apr;28(4):505-14. Epub 2014 Nov 14 doi: 10.1038/modpathol.2014.143. PMID: 25394778
POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium.
Meng B, Hoang LN, McIntyre JB, Duggan MA, Nelson GS, Lee CH, Köbel M
Gynecol Oncol 2014 Jul;134(1):15-9. Epub 2014 May 16 doi: 10.1016/j.ygyno.2014.05.006. PMID: 24844595

Diagnosis

Endometrial Carcinomas with a "Serous" Component in Young Women Are Enriched for DNA Mismatch Repair Deficiency, Lynch Syndrome, and POLE Exonuclease Domain Mutations.
Conlon N, Da Cruz Paula A, Ashley CW, Segura S, De Brot L, da Silva EM, Soslow RA, Weigelt B, DeLair DF
Am J Surg Pathol 2020 May;44(5):641-648. doi: 10.1097/PAS.0000000000001461. PMID: 32205482Free PMC Article
Rationale and design of the POLEM trial: avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III mismatch repair deficient or POLE exonuclease domain mutant colon cancer: a phase III randomised study.
Lau D, Kalaitzaki E, Church DN, Pandha H, Tomlinson I, Annels N, Gerlinger M, Sclafani F, Smith G, Begum R, Crux R, Gillbanks A, Wordsworth S, Chau I, Starling N, Cunningham D, Dhillon T
ESMO Open 2020 Feb;5(1) doi: 10.1136/esmoopen-2019-000638. PMID: 32079623Free PMC Article
p53, Mismatch Repair Protein, and POLE Abnormalities in Ovarian Clear Cell Carcinoma: An Outcome-based Clinicopathologic Analysis.
Parra-Herran C, Bassiouny D, Lerner-Ellis J, Olkhov-Mitsel E, Ismiil N, Hogen L, Vicus D, Nofech-Mozes S
Am J Surg Pathol 2019 Dec;43(12):1591-1599. doi: 10.1097/PAS.0000000000001328. PMID: 31335355
Dedifferentiated endometrial carcinomas with neuroendocrine features: a clinicopathologic, immunohistochemical, and molecular genetic study.
Espinosa I, De Leo A, D'Angelo E, Rosa-Rosa JM, Corominas M, Gonzalez A, Palacios J, Prat J
Hum Pathol 2018 Feb;72:100-106. Epub 2017 Nov 11 doi: 10.1016/j.humpath.2017.11.006. PMID: 29133142
Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.
Köbel M, Meng B, Hoang LN, Almadani N, Li X, Soslow RA, Gilks CB, Lee CH
Am J Surg Pathol 2016 Feb;40(2):166-180. doi: 10.1097/PAS.0000000000000536. PMID: 26492180Free PMC Article

Therapy

Clinico-pathological features associated with mismatch repair deficiency in endometrial undifferentiated/dedifferentiated carcinoma: A systematic review and meta-analysis.
Travaglino A, Raffone A, Gencarelli A, Saracinelli S, Riccardi C, Mollo A, Zullo F, Insabato L
Gynecol Oncol 2021 Feb;160(2):579-585. Epub 2020 Dec 1 doi: 10.1016/j.ygyno.2020.11.015. PMID: 33276986
Rationale and design of the POLEM trial: avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III mismatch repair deficient or POLE exonuclease domain mutant colon cancer: a phase III randomised study.
Lau D, Kalaitzaki E, Church DN, Pandha H, Tomlinson I, Annels N, Gerlinger M, Sclafani F, Smith G, Begum R, Crux R, Gillbanks A, Wordsworth S, Chau I, Starling N, Cunningham D, Dhillon T
ESMO Open 2020 Feb;5(1) doi: 10.1136/esmoopen-2019-000638. PMID: 32079623Free PMC Article

Prognosis

Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma.
Kobayashi Kato M, Asami Y, Takayanagi D, Matsuda M, Shimada Y, Hiranuma K, Kuno I, Komatsu M, Hamamoto R, Matsumoto K, Ishikawa M, Kohno T, Kato T, Shiraishi K, Yoshida H
Cancer Sci 2022 May;113(5):1712-1721. Epub 2022 Mar 24 doi: 10.1111/cas.15328. PMID: 35278272Free PMC Article
Molecular characterization in the prediction of disease extent in endometrial carcinoma.
Kolehmainen AM, Pasanen AM, Koivisto-Korander RL, Bützow RC, Loukovaara MJ
Eur J Obstet Gynecol Reprod Biol 2021 Jan;256:478-483. Epub 2020 Oct 16 doi: 10.1016/j.ejogrb.2020.10.031. PMID: 33189427
Endometrial Carcinomas with a "Serous" Component in Young Women Are Enriched for DNA Mismatch Repair Deficiency, Lynch Syndrome, and POLE Exonuclease Domain Mutations.
Conlon N, Da Cruz Paula A, Ashley CW, Segura S, De Brot L, da Silva EM, Soslow RA, Weigelt B, DeLair DF
Am J Surg Pathol 2020 May;44(5):641-648. doi: 10.1097/PAS.0000000000001461. PMID: 32205482Free PMC Article
Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.
Köbel M, Meng B, Hoang LN, Almadani N, Li X, Soslow RA, Gilks CB, Lee CH
Am J Surg Pathol 2016 Feb;40(2):166-180. doi: 10.1097/PAS.0000000000000536. PMID: 26492180Free PMC Article
POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium.
Meng B, Hoang LN, McIntyre JB, Duggan MA, Nelson GS, Lee CH, Köbel M
Gynecol Oncol 2014 Jul;134(1):15-9. Epub 2014 May 16 doi: 10.1016/j.ygyno.2014.05.006. PMID: 24844595

Clinical prediction guides

Clinical impact of genetic alterations of CTNNB1 in patients with grade 3 endometrial endometrioid carcinoma.
Kobayashi Kato M, Asami Y, Takayanagi D, Matsuda M, Shimada Y, Hiranuma K, Kuno I, Komatsu M, Hamamoto R, Matsumoto K, Ishikawa M, Kohno T, Kato T, Shiraishi K, Yoshida H
Cancer Sci 2022 May;113(5):1712-1721. Epub 2022 Mar 24 doi: 10.1111/cas.15328. PMID: 35278272Free PMC Article
Molecular characterization in the prediction of disease extent in endometrial carcinoma.
Kolehmainen AM, Pasanen AM, Koivisto-Korander RL, Bützow RC, Loukovaara MJ
Eur J Obstet Gynecol Reprod Biol 2021 Jan;256:478-483. Epub 2020 Oct 16 doi: 10.1016/j.ejogrb.2020.10.031. PMID: 33189427
Endometrial Carcinomas with a "Serous" Component in Young Women Are Enriched for DNA Mismatch Repair Deficiency, Lynch Syndrome, and POLE Exonuclease Domain Mutations.
Conlon N, Da Cruz Paula A, Ashley CW, Segura S, De Brot L, da Silva EM, Soslow RA, Weigelt B, DeLair DF
Am J Surg Pathol 2020 May;44(5):641-648. doi: 10.1097/PAS.0000000000001461. PMID: 32205482Free PMC Article
Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.
Köbel M, Meng B, Hoang LN, Almadani N, Li X, Soslow RA, Gilks CB, Lee CH
Am J Surg Pathol 2016 Feb;40(2):166-180. doi: 10.1097/PAS.0000000000000536. PMID: 26492180Free PMC Article
POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium.
Meng B, Hoang LN, McIntyre JB, Duggan MA, Nelson GS, Lee CH, Köbel M
Gynecol Oncol 2014 Jul;134(1):15-9. Epub 2014 May 16 doi: 10.1016/j.ygyno.2014.05.006. PMID: 24844595

Recent systematic reviews

Clinico-pathological features associated with mismatch repair deficiency in endometrial undifferentiated/dedifferentiated carcinoma: A systematic review and meta-analysis.
Travaglino A, Raffone A, Gencarelli A, Saracinelli S, Riccardi C, Mollo A, Zullo F, Insabato L
Gynecol Oncol 2021 Feb;160(2):579-585. Epub 2020 Dec 1 doi: 10.1016/j.ygyno.2020.11.015. PMID: 33276986

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