Germline mutations of the APC gene, which encodes a multidomain protein of 2843 amino acid residues, cause familial adenomatous polyposis (FAP). Three FAP clinical variants are correlated with the location of APC mutations: (1) classic FAP with profuse polyposis (>1000 adenomas), associated with mutations from codon 1250 to 1424; (2) attenuated FAP (<100 adenomas), associated with mutations at APC extremities (before codon 157 and after codon 1595); (3) classic FAP with intermediate colonic polyposis (100–1000 adenomas), associated with mutations located in the remaining part of APC. In an effort to decipher the clinical phenotype associated with APC C-terminal germline truncating mutations in patients with FAP, after screening APC mutations in one family whose members (n=4) developed gastric polyposis, colon oligo-polyposis and desmoid tumours, we performed a literature meta-analysis of clinically characterised patients (n=97) harbouring truncating mutations in APC C-terminus. The APC distal mutations identified in this study cluster with a phenotype characterised by colon oligo-polyposis, diffuse gastric polyposis and desmoid tumours. In conclusion, we describe a novel FAP clinical variant, which we propose to refer to as Gastric Polyposis and Desmoid FAP, that may require tailored management.
- APC C-terminus
- Gastric Polyposis
- Familial Adenomatous Polyposis
- Gastric Polyposis and Desmoid FAP
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Contributors VD, IL and CS conceived and designed the study, performed data analysis, wrote and revised the manuscript for important intellectual content. CF performed statistical analysis, reviewed the data and helped to write the manuscript. FC, GF, VG, PS and MLS acquired the literature data and analysed and interpreted the data. NR and AS performed genetic analysis and reviewed the data and manuscript for important intellectual content. CL provided clinical data. All the authors reviewed the manuscript.
Funding This work was supported by the Italian Ministry of Health ‘Ricerca Corrente 2017-2019’ to IL, ‘Ricerca Corrente 2018–2020; 2019–2021’ to CS; by PRIN - Research Projects of National Relevance (PRIN 2017, n. 2017WNKSLR-LS4) from the Italian MIUR to CS and by Fondazione Puglia (grant ‘Ricerca di nuovi geni di predisposizione e di markers predittivi di neoplasia nelle sindromi di predisposizione ereditaria al cancro del colon retto’) to AS.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.