β-catenin mutations in sporadic fundic gland polyps

Shigeki Sekine, Tatsuhiro Shibata, Yuko Yamauchi, Yukihiro Nakanishi, Tadakazu Shimoda, Michiie Sakamoto, Setsuo Hirohashi

研究成果: Article

49 引用 (Scopus)

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Fundic gland polyp (FGP) is the most common gastric polyp. It occurs sporadically or in association with familial adenomatous polyposis (FAP). FAP patients carry germline mutations of the adenomatous polyposis coli (APC) gene, and previous studies have revealed frequent somatic mutations of the APC gene in FGPs associated with FAP. Although inactivation of the APC gene contributes to histogenesis of FGPs associated with FAP, this rarely happens in sporadic cases. Loss of the APC gene promotes abnormal accumulation of β-catenin, and mutation of GSK-3β phosphorylation sites in the β-catenin gene can have a similar effect. To elucidate the contribution of β-catenin gene mutation to the histogenesis of sporadic FGP, we analyzed β-catenin gene mutation in exon 3 in 45 FGP lesions obtained from 35 patients. Somatic mutations were found in 29 lesions: 28 were missense mutations and one was an in-frame deletion. All of the missense mutations were confined to the former two serine residues of the GSK-3β phosphorylation sites and their flanking residues (codons 32, 33, 34, 37). Analysis in cases with multiple FGPs revealed a different mutation in each lesion, indicating their multicentric origin. Therefore, a significant proportion of sporadic FGPs have genetic alterations involving β-catenin stabilization, as did FAP-associated FGPs.

元の言語English
ページ(範囲)381-386
ページ数6
ジャーナルVirchows Archiv
440
発行部数4
DOI
出版物ステータスPublished - 2002 4 27
外部発表Yes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Sekine, S., Shibata, T., Yamauchi, Y., Nakanishi, Y., Shimoda, T., Sakamoto, M., & Hirohashi, S. (2002). β-catenin mutations in sporadic fundic gland polyps. Virchows Archiv, 440(4), 381-386. https://doi.org/10.1007/s004280100527