Frequent <i><scp>GNAS</scp></i> and <i><scp>KRAS</scp></i> mutations in pyloric gland adenoma of the stomach and duodenum

<jats:title>Abstract</jats:title><jats:p><jats:bold>Gastric and duodenal adenomas exhibit a significant morphological and phenotypical diversity and are classified into intestinal‐type, foveolar‐type and pyloric gland adenomas. We analysed the mutations in <jats:italic><jats:styled-content style="fixed-case">GNAS</jats:styled-content></jats:italic>, <jats:italic><jats:styled-content style="fixed-case">KRAS</jats:styled-content></jats:italic>, <jats:italic><jats:styled-content style="fixed-case">BRAF</jats:styled-content></jats:italic> and <jats:italic><jats:styled-content style="fixed-case">CTNNB1</jats:styled-content></jats:italic> and the expressions of mismatch repair (<jats:styled-content style="fixed-case">MMR</jats:styled-content>) proteins in 80 gastric and 32 duodenal adenomas with histologically distinct subtypes, as well as in 71 gastric adenocarcinomas. Activating <jats:italic><jats:styled-content style="fixed-case">GNAS</jats:styled-content></jats:italic> mutations were found in 22 of the 35 pyloric gland adenomas (<jats:styled-content style="fixed-case">PGAs</jats:styled-content>; 63%) but in none of the foveolar‐type or intestinal‐type adenomas or the adenocarcinomas. Fourteen <jats:styled-content style="fixed-case">PGAs</jats:styled-content> (41%), two foveolar‐type adenomas (9%), five intestinal‐type adenomas (9%) and one adenocarcinoma (1%) had <jats:italic><jats:styled-content style="fixed-case">KRAS</jats:styled-content></jats:italic> mutations. <jats:italic><jats:styled-content style="fixed-case">BRAF</jats:styled-content></jats:italic> mutations were absent in all the adenomas and adenocarcinomas that were examined. <jats:italic><jats:styled-content style="fixed-case">CTNNB1</jats:styled-content></jats:italic> mutations were only found in two intestinal‐type adenomas (4%). Notably, 13 of the 14 <jats:italic><jats:styled-content style="fixed-case">KRAS</jats:styled-content></jats:italic>‐mutated gastric and duodenal <jats:styled-content style="fixed-case">PGAs</jats:styled-content> had concurrent <jats:italic><jats:styled-content style="fixed-case">GNAS</jats:styled-content></jats:italic> mutations. The loss of the <jats:styled-content style="fixed-case">MMR</jats:styled-content> proteins, which is indicative of microsatellite instability, was observed in one <jats:styled-content style="fixed-case">PGA</jats:styled-content> (3%), 12 foveolar‐type adenomas (52%), one intestinal‐type adenoma (2%) and five adenocarcinomas (7%). These observations indicate that each histological subtype of gastric and duodenal adenomas has a distinct genetic background. In particular, the present study identified the frequent presence of activating <jats:italic><jats:styled-content style="fixed-case">GNAS</jats:styled-content></jats:italic> mutations, which are often associated with <jats:italic><jats:styled-content style="fixed-case">KRAS</jats:styled-content></jats:italic> mutations, as a characteristic genetic feature of <jats:styled-content style="fixed-case">PGAs</jats:styled-content> of the stomach and duodenum.</jats:bold></jats:p>