Entry

H02568                      Disease

Name

Polymerase proofreading-associated polyposis

Supergrp

Colorectal cancer [DS:H00020]
Solid tumor [DS:H02421]

Description

Polymerase proofreading-associated polyposis (PPAP) is an autosomal dominant cancer syndrome caused by germline variants in the exonuclease domains of POLD1 and POLE. PPAP is characterized by oligo adenomatous polyposis and increased risk of colorectal cancer, endometrial cancer and brain tumors.

Category

Cancer

Brite

Human diseases [BR:br08402]
Cancers
  Cancers of the digestive system
   H02568  Polymerase proofreading-associated polyposis
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
  Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
   Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
    Malignant neoplasms of digestive organs
     Malignant neoplasms of intestine
      Malignant neoplasms of large intestine
       2B90  Malignant neoplasms of colon
        H02568  Polymerase proofreading-associated polyposis

Related
pathway

hsa03410

Base excision repair

hsa03420

Nucleotide excision repair

hsa03430

Mismatch repair

hsa03030

DNA replication

Network

nt06503 Mismatch repair
nt06504 Base excision repair

Gene

POLD1 [HSA:5424] [KO:K02327]
POLE [HSA:5426] [KO:K02324]

Other DBs

ICD-11:

2B90.Y

ICD-10:

C18.9

OMIM:

612591 615083

Reference

PMID:33948826

Authors

Palles C, Martin L, Domingo E, Chegwidden L, McGuire J, Cuthill V, Heitzer E, Kerr R, Kerr D, Kearsey S, Clark SK, Tomlinson I, Latchford A

Title

The clinical features of polymerase proof-reading associated polyposis (PPAP) and recommendations for patient management.

Journal

Fam Cancer 21:197-209 (2022)
DOI:10.1007/s10689-021-00256-y

Reference

PMID:26133394

Authors

Bellido F, Pineda M, Aiza G, Valdes-Mas R, Navarro M, Puente DA, Pons T, Gonzalez S, Iglesias S, Darder E, Pinol V, Soto JL, Valencia A, Blanco I, Urioste M, Brunet J, Lazaro C, Capella G, Puente XS, Valle L

Title

POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance.

Journal

Genet Med 18:325-32 (2016)
DOI:10.1038/gim.2015.75

Reference

PMID:32548621 (POLD1)

Authors

Ito T, Nomizu T, Eguchi H, Kamae N, Dechamethakun S, Akama Y, Endo G, Sugano K, Yoshida T, Okazaki Y, Ishida H

Title

The first case report of polymerase proofreading-associated polyposis in POLD1 variant, c.1433G>A p.S478N, in Japan.

Journal

Jpn J Clin Oncol 50:1080-1083 (2020)
DOI:10.1093/jjco/hyaa090

Reference

PMID:32424176 (POLE)

Authors

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

Title

Genetic, structural, and functional characterization of POLE polymerase proofreading variants allows cancer risk prediction.

Journal

Genet Med 22:1533-1541 (2020)
DOI:10.1038/s41436-020-0828-z

DISEASE: Polymerase proofreading-associated polyposis