POLE and neoplasm: Germline PVs in APC underlie the majority of adenomatous polyposis cases, followed by biallelic MUTYH PVs, and to a much lesser extent, PVs in the exonuclease domain of POLE or POLD1. Each adenomatous polyposis syndrome has its own distinct phenotypic features including variations in onset age, risks for different extracolonic cancers, clinical manifestations, and tumour molecular characteristics.