Familial adenomatous polyposis‐associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features

Aims Familial adenomatous polyposis ( FAP ) is a hereditary cancer predisposition syndrome caused by a germline APC mutation. A recent study showed the enrichment of pyloric gland adenomas ( PGA s) of the stomach, in addition to fundic gland polyps ( FGP s) and foveolar‐type adenomas ( FA s), in patients with FAP . In the present study, we analysed the genetic alterations in these FAP ‐associated gastric lesions. Methods and results Mutational statuses of GNAS and KRAS , which are frequently mutated in sporadic PGA s, as well as those of APC , were examined in PGA s, FA s and FGP s in patients with FAP using Sanger sequencing. Our analysis identified GNAS mutations in five of six PGA s (83%), but in none of the three FA s or the 40 FGP s examined. KRAS mutations were identified in four PGA s (67%), one FA (33%) and one FGP (3%). Somatic truncating APC mutations were found in all PGA s (100%), two FA s (67%) and 14 FGP s (47%). We additionally analysed sporadic PGA s of the stomach and duodenum and identified truncating APC mutations in 11 of 25 lesions (44%). Conclusions FAP ‐associated and sporadic PGA s not only show similar morphologies, but also share common genetic aberrations, including mutations of GNAS , KRAS and APC .