The Desmoid Tumor Research Foundation

October 2019

Gastric polyposis and desmoid tumours as a new familial adenomatous polyposis clinical variant associated with APC mutation at the extreme 3′-end

Author Information

Disciglio V(1), Fasano C(1), Cariola F(1), Forte G(1), Grossi V(1), Sanese P(2), Lepore Signorile M(1)(3), Resta N(2), Lotesoriere C(4), Stella A(2), Lolli I(4), Simone C(1)(2).

(1)Medical Genetics, National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy. (2)Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO),University of Bari "Aldo Moro", Bari, Italy. (3)Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy. (4)Department of Oncology, National Institute of Gastroenterology "S. de Bellis",Research Hospital, Castellana Grotte, Italy.

Publication

J Med Genet

Summary

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.

View Abstract