{"entity":{"id":"polymerase-proofreading-associated-polyposis","kind":"term","name":"Polymerase proofreading-associated polyposis","aka":["POLE polyposis","POLD1 polyposis","polymerase proofreading-related polyposis"],"tldr":"Polymerase proofreading-associated polyposis is a rare inherited condition, caused by a fault in the proofreading part of the POLE or POLD1 gene, that causes bowel polyps and early bowel cancer, and womb cancer with POLD1. Care is planned at a specialist centre because there are too few patients for a fixed schedule.","summary":"Autosomal dominant. Palles 2013 (Nature Genetics) found the high-penetrance heterozygous variants POLE p.Leu424Val and POLD1 p.Ser478Asn in families with multiple adenomas and early colorectal cancer; POLD1 was also associated with endometrial cancer. The tumours are microsatellite stable and hypermutated by base substitutions.\n\nBSG 2020 found insufficient clinical data for specific guidance and recommends referral to a multidisciplinary expert centre (weak recommendation, low evidence). The AACR 2024 update groups it with Lynch syndrome and constitutional mismatch repair deficiency as replication repair deficiency syndromes, and notes aggressive brain tumours in some children with these syndromes and the response of hypermutant cancers to checkpoint immunotherapy.","asOf":"2026-11-04","wikipedia":"https://en.wikipedia.org/wiki/Polymerase_proofreading-associated_polyposis","links":[{"label":"Monahan, Gut 2020: BSG, ACPGBI and UKCGG guidelines for the management of hereditary colorectal cancer","url":"https://doi.org/10.1136/gutjnl-2019-319915"},{"label":"Das, Clin Cancer Res 2024: DNA replication repair deficiency syndromes in children and young adults (AACR update)","url":"https://doi.org/10.1158/1078-0432.ccr-23-3994"},{"label":"Orphanet ORPHA:447877","url":"https://www.orpha.net/en/disease/detail/447877"}],"tags":["gap-fill","hereditary"],"related":[],"cancers":["colorectal","endometrial"],"sections":[],"technologies":["germline-testing"],"targets":["pole","pold1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["colonoscopy","hereditary-cancer-syndromes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-palles-germline-pole-pold1-proofreading-nat-genet-2013"],"journals":[],"dependsOn":[],"notes":["Orphanet ORPHA:447877. In the NHS directory it is tested under R211, inherited polyposis."],"category":"Genomics & genetics"},"route":"/terms/polymerase-proofreading-associated-polyposis/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"target":[{"id":"pold1","kind":"target","name":"POLD1","route":"/targets/pold1/"},{"id":"pole","kind":"target","name":"POLE","route":"/targets/pole/"}],"term":[{"id":"colonoscopy","kind":"term","name":"Colonoscopy","route":"/terms/colonoscopy/"},{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"}],"paper":[{"id":"paper-palles-germline-pole-pold1-proofreading-nat-genet-2013","kind":"paper","name":"Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas","route":"/key-papers/paper-palles-germline-pole-pold1-proofreading-nat-genet-2013/"}]}}