Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features

Taiki Hashimoto, Reiko Ogawa, Akiko Matsubara, Hirokazu Taniguchi, Kokichi Sugano, Mineko Ushiama, Teruhiko Yoshida, Yae Kanai, Shigeki Sekine

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Aims: Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome caused by a germline APC mutation. A recent study showed the enrichment of pyloric gland adenomas (PGAs) of the stomach, in addition to fundic gland polyps (FGPs) and foveolar-type adenomas (FAs), in patients with FAP. In the present study, we analysed the genetic alterations in these FAP-associated gastric lesions. Methods and results: Mutational statuses of GNAS and KRAS, which are frequently mutated in sporadic PGAs, as well as those of APC, were examined in PGAs, FAs and FGPs in patients with FAP using Sanger sequencing. Our analysis identified GNAS mutations in five of six PGAs (83%), but in none of the three FAs or the 40 FGPs examined. KRAS mutations were identified in four PGAs (67%), one FA (33%) and one FGP (3%). Somatic truncating APC mutations were found in all PGAs (100%), two FAs (67%) and 14 FGPs (47%). We additionally analysed sporadic PGAs of the stomach and duodenum and identified truncating APC mutations in 11 of 25 lesions (44%). Conclusions: FAP-associated and sporadic PGAs not only show similar morphologies, but also share common genetic aberrations, including mutations of GNAS, KRAS and APC.

Original languageEnglish
Pages (from-to)689-698
Number of pages10
JournalHistopathology
Volume67
Issue number5
DOIs
Publication statusPublished - 2015 Nov 1
Externally publishedYes

Fingerprint

Adenomatous Polyposis Coli
Upper Gastrointestinal Tract
Gastric Mucosa
Adenoma
Polyps
Mutation
Stomach
Hereditary Neoplastic Syndromes
Germ-Line Mutation
Duodenum

Keywords

  • APC
  • Familial adenomatous polyposis
  • Fundic gland polyp
  • GNAS
  • KRAS
  • Pyloric gland adenoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features. / Hashimoto, Taiki; Ogawa, Reiko; Matsubara, Akiko; Taniguchi, Hirokazu; Sugano, Kokichi; Ushiama, Mineko; Yoshida, Teruhiko; Kanai, Yae; Sekine, Shigeki.

In: Histopathology, Vol. 67, No. 5, 01.11.2015, p. 689-698.

Research output: Contribution to journalArticle

Hashimoto, T, Ogawa, R, Matsubara, A, Taniguchi, H, Sugano, K, Ushiama, M, Yoshida, T, Kanai, Y & Sekine, S 2015, 'Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features', Histopathology, vol. 67, no. 5, pp. 689-698. https://doi.org/10.1111/his.12705
Hashimoto, Taiki ; Ogawa, Reiko ; Matsubara, Akiko ; Taniguchi, Hirokazu ; Sugano, Kokichi ; Ushiama, Mineko ; Yoshida, Teruhiko ; Kanai, Yae ; Sekine, Shigeki. / Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features. In: Histopathology. 2015 ; Vol. 67, No. 5. pp. 689-698.
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AU - Sugano, Kokichi

AU - Ushiama, Mineko

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AU - Kanai, Yae

AU - Sekine, Shigeki

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N2 - Aims: Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome caused by a germline APC mutation. A recent study showed the enrichment of pyloric gland adenomas (PGAs) of the stomach, in addition to fundic gland polyps (FGPs) and foveolar-type adenomas (FAs), in patients with FAP. In the present study, we analysed the genetic alterations in these FAP-associated gastric lesions. Methods and results: Mutational statuses of GNAS and KRAS, which are frequently mutated in sporadic PGAs, as well as those of APC, were examined in PGAs, FAs and FGPs in patients with FAP using Sanger sequencing. Our analysis identified GNAS mutations in five of six PGAs (83%), but in none of the three FAs or the 40 FGPs examined. KRAS mutations were identified in four PGAs (67%), one FA (33%) and one FGP (3%). Somatic truncating APC mutations were found in all PGAs (100%), two FAs (67%) and 14 FGPs (47%). We additionally analysed sporadic PGAs of the stomach and duodenum and identified truncating APC mutations in 11 of 25 lesions (44%). Conclusions: FAP-associated and sporadic PGAs not only show similar morphologies, but also share common genetic aberrations, including mutations of GNAS, KRAS and APC.

AB - Aims: Familial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome caused by a germline APC mutation. A recent study showed the enrichment of pyloric gland adenomas (PGAs) of the stomach, in addition to fundic gland polyps (FGPs) and foveolar-type adenomas (FAs), in patients with FAP. In the present study, we analysed the genetic alterations in these FAP-associated gastric lesions. Methods and results: Mutational statuses of GNAS and KRAS, which are frequently mutated in sporadic PGAs, as well as those of APC, were examined in PGAs, FAs and FGPs in patients with FAP using Sanger sequencing. Our analysis identified GNAS mutations in five of six PGAs (83%), but in none of the three FAs or the 40 FGPs examined. KRAS mutations were identified in four PGAs (67%), one FA (33%) and one FGP (3%). Somatic truncating APC mutations were found in all PGAs (100%), two FAs (67%) and 14 FGPs (47%). We additionally analysed sporadic PGAs of the stomach and duodenum and identified truncating APC mutations in 11 of 25 lesions (44%). Conclusions: FAP-associated and sporadic PGAs not only show similar morphologies, but also share common genetic aberrations, including mutations of GNAS, KRAS and APC.

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