TY - JOUR
T1 - Sporadic fundic gland polyps
T2 - Common gastric polyps arising through activating mutations in the β-catenin gene
AU - Abraham, Susan C.
AU - Nobukawa, Bunsei
AU - Giardiello, Francis M.
AU - Hamilton, Stanley R.
AU - Wu, Tsung Teh
N1 - Funding Information:
Supported in part by an award from BioNumerik Pharmaceuticals, Inc. (to S. C. A.).
PY - 2001
Y1 - 2001
N2 - Fundic gland polyps (FGPs) are the most common gastric polyps. FGPs traditionally have been regarded as nondysplastic hamartomatous or hyperplastic lesions, but their pathogenesis remains unclear. We have recently shown that somatic adenomatous polyposis coli (APC) gene alterations are frequently present in FGPs associated with familial adenomatous polyposis (FAP), raising the possibility that mutations of the β-catenin gene affecting the APC/β-catenin pathway might be involved in the pathogenesis of sporadic FGPs. We analyzed somatic β-catenin gene mutations in 57 sporadic FGPs from 40 patients without FAP and in 19 FGPs from 13 FAP patients. Direct DNA sequencing of exon 3 encompassing the glycogen synthase kinase-3β phosphorylation region for β-catenin was used with confirmation by HinfI restriction endonuclease digestion. The foveolar epithelium and dilated fundic glands of the polyps were separately microdissected and analyzed in 22 of 57 sporadic FGPs. Activating β-catenin gene mutations were present in 91% (52 of 57) of sporadic FGPs. Both the foveolar epithelium and the dilated fundic gland epithelium comprising the polyps were shown to have the same somatic β-catenin mutation in 21 of 22 (95%) sporadic FGPs. In contrast, β-catenin gene mutations were not present in any of the 19 FAP-associated FGPs (P < 0.000001). The high frequency of β-catenin mutations in sporadic FGPs indicates that these lesions arise through activating mutations of the β-catenin gene. β-catenin mutations in gastrointestinal tract polyps have previously only been demonstrated in a subset of adenomatous (dysplastic) or neoplastic polyps. Sporadic FGPs are therefore the only lesions of the gastrointestinal tract to demonstrate β-catenin mutations while lacking dysplastic morphology.
AB - Fundic gland polyps (FGPs) are the most common gastric polyps. FGPs traditionally have been regarded as nondysplastic hamartomatous or hyperplastic lesions, but their pathogenesis remains unclear. We have recently shown that somatic adenomatous polyposis coli (APC) gene alterations are frequently present in FGPs associated with familial adenomatous polyposis (FAP), raising the possibility that mutations of the β-catenin gene affecting the APC/β-catenin pathway might be involved in the pathogenesis of sporadic FGPs. We analyzed somatic β-catenin gene mutations in 57 sporadic FGPs from 40 patients without FAP and in 19 FGPs from 13 FAP patients. Direct DNA sequencing of exon 3 encompassing the glycogen synthase kinase-3β phosphorylation region for β-catenin was used with confirmation by HinfI restriction endonuclease digestion. The foveolar epithelium and dilated fundic glands of the polyps were separately microdissected and analyzed in 22 of 57 sporadic FGPs. Activating β-catenin gene mutations were present in 91% (52 of 57) of sporadic FGPs. Both the foveolar epithelium and the dilated fundic gland epithelium comprising the polyps were shown to have the same somatic β-catenin mutation in 21 of 22 (95%) sporadic FGPs. In contrast, β-catenin gene mutations were not present in any of the 19 FAP-associated FGPs (P < 0.000001). The high frequency of β-catenin mutations in sporadic FGPs indicates that these lesions arise through activating mutations of the β-catenin gene. β-catenin mutations in gastrointestinal tract polyps have previously only been demonstrated in a subset of adenomatous (dysplastic) or neoplastic polyps. Sporadic FGPs are therefore the only lesions of the gastrointestinal tract to demonstrate β-catenin mutations while lacking dysplastic morphology.
UR - http://www.scopus.com/inward/record.url?scp=0035103118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035103118&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64047-3
DO - 10.1016/S0002-9440(10)64047-3
M3 - Article
C2 - 11238048
AN - SCOPUS:0035103118
SN - 0002-9440
VL - 158
SP - 1005
EP - 1010
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -