Genetic alteration of colorectal adenoma‐carcinoma sequence among gastric adenocarcinoma and dysplastic lesions in a patient with attenuated familial adenomatous polyposis

Abstract

Abstract Background Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and adenocarcinoma that is frequently accompanied by extracolonic neoplasm. The risk of gastric carcinoma is increasing in Western FAP patients as well as Asian patients. Methods We report the case of an FAP patient with fundic gland polyposis who developed gastric adenocarcinoma and metachronous pyloric gland adenomas. These tumors were endoscopically resected, and immunohistochemistry with gastric mucin (i.e., MUC6, MUC5AC) showed that the tumors belonged to the gastric subtype. Somatic mutation profiles were determined by target amplicon sequencing using a next‐generation sequencer. Results Germline APC variant c.5782delC was found by direct sequencing and somatic KRAS mutations in these tumors were identified by next‐generation sequencing. Different KRAS mutation alleles (KRAS p.Gly12Ala, p.Gly12Arg, and p.Gly12Asp) indicated these dysplastic lesions developed from a distinct origin in fundic gland polyposis. Sequential mutations of the APC and KRAS were judged—based on a database search—to be characteristic of the adenoma‐carcinoma sequence in colorectal carcinogenesis. Conclusion The colonic adenoma‐carcinoma sequence among gastric adenocarcinoma and dysplastic lesions was indicated in FAP‐associated gastric carcinogenesis.

Keywords

• endoscopic submucosal dissection
• fundic gland polyp
• gastric cancer
• next‐generation sequencing
• somatic mutation