Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum. Issue 4 (4th February 2013)

• Record Type: Journal Article
• Authors: Matsubara, Akiko; Sekine, Shigeki; Kushima, Ryoji; Ogawa, Reiko; Taniguchi, Hirokazu; Tsuda, Hitoshi; Kanai, Yae
• Is Part Of: Journal of pathology. Volume 229:Issue 4(2013)
• Page Start: 579
• Page End: 587
• Publication Date: 2013-02-04
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4153
• Languages: English
• ISSNs: 0022-3417

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p> <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 <italic>GNAS</italic>, <italic>KRAS</italic>, <italic>BRAF</italic> and <italic>CTNNB1</italic> and the expressions of mismatch repair (MMR) proteins in 80 gastric and 32 duodenal adenomas with histologically distinct subtypes, as well as in 71 gastric adenocarcinomas. Activating <italic>GNAS</italic> mutations were found in 22 of the 35 pyloric gland adenomas (PGAs; 63%) but in none of the foveolar‐type or intestinal‐type adenomas or the adenocarcinomas. Fourteen PGAs (41%), two foveolar‐type adenomas (9%), five intestinal‐type adenomas (9%) and one adenocarcinoma (1%) had <italic>KRAS</italic> mutations. <italic>BRAF</italic> mutations were absent in all the adenomas and adenocarcinomas that were examined. <italic>CTNNB1</italic> mutations were only found in two intestinal‐type adenomas (4%). Notably, 13 of the 14 <italic>KRAS</italic>‐mutated gastric and duodenal PGAs had concurrent <italic>GNAS</italic> mutations. The loss of the MMR proteins, which is indicative of microsatellite instability, was observed in one PGA (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 <italic>GNAS</italic> mutations, which are often associated with <italic>KRAS</italic> mutations, as a characteristic genetic feature of PGAs of the stomach and duodenum.</bold> </p> </abstract>