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Polymerase proofreading associated polyposis

MedGen UID:
1687472
•Concept ID:
C5202613
•
Disease or Syndrome
Synonym: Polymerase Proofreading Associated Polyposis

Definition

An autosomal dominant condition caused by mutation(s) in the POLE and/or POLD1 genes, encoding DNA polymerase epsilon catalytic subunit A and DNA polymerase delta catalytic subunit, respectively. It is characterized by colorectal polyposis and a predisposition to colorectal cancer. Mutation(s) in POLE and/or POLD1 genes have been associated with an increased risk of endometrial cancer, breast and brain tumors, and multi-tumor phenotypes. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Polymerase proofreading associated polyposis

Professional guidelines

PubMed

Genetic testing for inherited colorectal cancer and polyposis, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).
Mao R, Krautscheid P, Graham RP, Ganguly A, Shankar S, Ferber M, Hegde M; ACMG Laboratory Quality Assurance Committee
Genet Med 2021 Oct;23(10):1807-1817. Epub 2021 Jun 17 doi: 10.1038/s41436-021-01207-9. PMID: 34140662

Recent clinical studies

Etiology

Characterization of POLE c.1373A > T p.(Tyr458Phe), causing high cancer risk.
Rocque MJ, Leipart V, Kumar Singh A, Mur P, Olsen MF, Engebretsen LF, Martin-Ramos E, Aligué R, Sætrom P, Valle L, Drabløs F, Otterlei M, Sjursen W
Mol Genet Genomics 2023 May;298(3):555-566. Epub 2023 Mar 1 doi: 10.1007/s00438-023-02000-w. PMID: 36856825Free PMC Article
Genetic, structural, and functional characterization of POLE polymerase proofreading variants allows cancer risk prediction.
Hamzaoui N, Alarcon F, Leulliot N, Guimbaud R, Buecher B, Colas C, Corsini C, Nuel G, Terris B, Laurent-Puig P, Chaussade S, Dhooge M, Madru C, Clauser E
Genet Med 2020 Sep;22(9):1533-1541. Epub 2020 May 19 doi: 10.1038/s41436-020-0828-z. PMID: 32424176
An Update on Inherited Colon Cancer and Gastrointestinal Polyposis.
Plevová P
Klin Onkol 2019 Summer;32(Supplementum2):97-108. doi: 10.14735/amko2019S97. PMID: 31409085
Update on genetic predisposition to colorectal cancer and polyposis.
Valle L, de Voer RM, Goldberg Y, Sjursen W, Försti A, Ruiz-Ponte C, Caldés T, Garré P, Olsen MF, Nordling M, Castellvi-Bel S, Hemminki K
Mol Aspects Med 2019 Oct;69:10-26. Epub 2019 Mar 18 doi: 10.1016/j.mam.2019.03.001. PMID: 30862463
Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602

Diagnosis

Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1.
Mur P, Viana-Errasti J, García-Mulero S, Magraner-Pardo L, Muñoz IG, Pons T, Capellá G, Pineda M, Feliubadaló L, Valle L
Genome Med 2023 Oct 17;15(1):85. doi: 10.1186/s13073-023-01234-y. PMID: 37848928Free PMC Article
Constitutional POLE variants causing a phenotype reminiscent of constitutional mismatch repair deficiency.
Sehested A, Meade J, Scheie D, Østrup O, Bertelsen B, Misiakou MA, Sarosiek T, Kessler E, Melchior LC, Munch-Petersen HF, Pai RK, Schmuth M, Gottschling H, Zschocke J, Gallon R, Wimmer K
Hum Mutat 2022 Jan;43(1):85-96. Epub 2021 Dec 2 doi: 10.1002/humu.24299. PMID: 34816535
An Update on Inherited Colon Cancer and Gastrointestinal Polyposis.
Plevová P
Klin Onkol 2019 Summer;32(Supplementum2):97-108. doi: 10.14735/amko2019S97. PMID: 31409085
The role of inherited genetic variants in colorectal polyposis syndromes.
Short E, Sampson J
Adv Genet 2019;103:183-217. Epub 2019 Jan 22 doi: 10.1016/bs.adgen.2018.11.002. PMID: 30904095
Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602

Therapy

Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602

Prognosis

Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1.
Mur P, Viana-Errasti J, García-Mulero S, Magraner-Pardo L, Muñoz IG, Pons T, Capellá G, Pineda M, Feliubadaló L, Valle L
Genome Med 2023 Oct 17;15(1):85. doi: 10.1186/s13073-023-01234-y. PMID: 37848928Free PMC Article
Role of POLE and POLD1 in familial cancer.
Mur P, García-Mulero S, Del Valle J, Magraner-Pardo L, Vidal A, Pineda M, Cinnirella G, Martín-Ramos E, Pons T, López-Doriga A, Belhadj S, Feliubadaló L, Munoz-Torres PM, Navarro M, Grau E, Darder E, Llort G, Sanz J, Ramón Y Cajal T, Balmana J, Brunet J, Moreno V, Piulats JM, Matías-Guiu X, Sanz-Pamplona R, Aligué R, Capellá G, Lázaro C, Valle L
Genet Med 2020 Dec;22(12):2089-2100. Epub 2020 Aug 14 doi: 10.1038/s41436-020-0922-2. PMID: 32792570Free PMC Article
Genetic, structural, and functional characterization of POLE polymerase proofreading variants allows cancer risk prediction.
Hamzaoui N, Alarcon F, Leulliot N, Guimbaud R, Buecher B, Colas C, Corsini C, Nuel G, Terris B, Laurent-Puig P, Chaussade S, Dhooge M, Madru C, Clauser E
Genet Med 2020 Sep;22(9):1533-1541. Epub 2020 May 19 doi: 10.1038/s41436-020-0828-z. PMID: 32424176
Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602
New genes emerging for colorectal cancer predisposition.
Esteban-Jurado C, Garre P, Vila M, Lozano JJ, Pristoupilova A, Beltrán S, Abulí A, Muñoz J, Balaguer F, Ocaña T, Castells A, Piqué JM, Carracedo A, Ruiz-Ponte C, Bessa X, Andreu M, Bujanda L, Caldés T, Castellví-Bel S
World J Gastroenterol 2014 Feb 28;20(8):1961-71. doi: 10.3748/wjg.v20.i8.1961. PMID: 24587672Free PMC Article

Clinical prediction guides

Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1.
Mur P, Viana-Errasti J, García-Mulero S, Magraner-Pardo L, Muñoz IG, Pons T, Capellá G, Pineda M, Feliubadaló L, Valle L
Genome Med 2023 Oct 17;15(1):85. doi: 10.1186/s13073-023-01234-y. PMID: 37848928Free PMC Article
Genomic landscape of colorectal carcinogenesis.
Kim JC, Bodmer WF
J Cancer Res Clin Oncol 2022 Mar;148(3):533-545. Epub 2022 Jan 20 doi: 10.1007/s00432-021-03888-w. PMID: 35048197
Role of POLE and POLD1 in familial cancer.
Mur P, García-Mulero S, Del Valle J, Magraner-Pardo L, Vidal A, Pineda M, Cinnirella G, Martín-Ramos E, Pons T, López-Doriga A, Belhadj S, Feliubadaló L, Munoz-Torres PM, Navarro M, Grau E, Darder E, Llort G, Sanz J, Ramón Y Cajal T, Balmana J, Brunet J, Moreno V, Piulats JM, Matías-Guiu X, Sanz-Pamplona R, Aligué R, Capellá G, Lázaro C, Valle L
Genet Med 2020 Dec;22(12):2089-2100. Epub 2020 Aug 14 doi: 10.1038/s41436-020-0922-2. PMID: 32792570Free PMC Article
Genetic, structural, and functional characterization of POLE polymerase proofreading variants allows cancer risk prediction.
Hamzaoui N, Alarcon F, Leulliot N, Guimbaud R, Buecher B, Colas C, Corsini C, Nuel G, Terris B, Laurent-Puig P, Chaussade S, Dhooge M, Madru C, Clauser E
Genet Med 2020 Sep;22(9):1533-1541. Epub 2020 May 19 doi: 10.1038/s41436-020-0828-z. PMID: 32424176
Current clinical topics of Lynch syndrome.
Tanakaya K
Int J Clin Oncol 2019 Sep;24(9):1013-1019. Epub 2018 May 9 doi: 10.1007/s10147-018-1282-7. PMID: 29744602

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