Limits...
Activating GNAS and KRAS mutations in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum.

Matsubara A, Ogawa R, Suzuki H, Oda I, Taniguchi H, Kanai Y, Kushima R, Sekine S - Br. J. Cancer (2015)

Bottom Line: The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%).A BRAF mutation was found in only one GFM lesion (2%).A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.

ABSTRACT

Background: Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds.

Methods: We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS, KRAS, and BRAF mutations.

Results: Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS-mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation.

Conclusions: A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours.

Show MeSH

Related in: MedlinePlus

GNAS and KRAS mutations in gastric foveolar metaplasia and gastric heterotopia. (A) Representative GNAS and KRAS mutations identified in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum. (B) GNAS mutations in each epithelial component of gastric heterotopia. An identical missense mutation is present in both the foveolar epithelium and oxyntic glands. Missense mutations are indicated by arrowheads. GNAS was sequenced using reverse primers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4402452&req=5

fig2: GNAS and KRAS mutations in gastric foveolar metaplasia and gastric heterotopia. (A) Representative GNAS and KRAS mutations identified in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum. (B) GNAS mutations in each epithelial component of gastric heterotopia. An identical missense mutation is present in both the foveolar epithelium and oxyntic glands. Missense mutations are indicated by arrowheads. GNAS was sequenced using reverse primers.

Mentions: Sequencing analyses identified activating GNAS mutations in 27 GFM lesions (41%), 23 GH lesions (28%), and 5 adenocarcinomas (17% Table 2, Figure 2A). Activating KRAS mutations were found in 17 GFM lesions (26%), 2 GH lesions (2%), and 11 adenocarcinomas (37%). An activating BRAF mutation was found only in one GFM lesion (2%). None of the normal duodenal mucosa specimens showed any genetic alterations. Taken together, 36 GFM lesions (55%), 23 GH lesions (28%), and 15 adenocarcinomas (50%) harboured at least one of these genetic alterations (Table 3). Multiple independent lesions of GFM or GH were analysed in 10 patients. Among them, the mutational statuses of the lesions were discordant in six patients, confirming the multifocality of these lesions (Table 4).


Activating GNAS and KRAS mutations in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum.

Matsubara A, Ogawa R, Suzuki H, Oda I, Taniguchi H, Kanai Y, Kushima R, Sekine S - Br. J. Cancer (2015)

GNAS and KRAS mutations in gastric foveolar metaplasia and gastric heterotopia. (A) Representative GNAS and KRAS mutations identified in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum. (B) GNAS mutations in each epithelial component of gastric heterotopia. An identical missense mutation is present in both the foveolar epithelium and oxyntic glands. Missense mutations are indicated by arrowheads. GNAS was sequenced using reverse primers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402452&req=5

fig2: GNAS and KRAS mutations in gastric foveolar metaplasia and gastric heterotopia. (A) Representative GNAS and KRAS mutations identified in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum. (B) GNAS mutations in each epithelial component of gastric heterotopia. An identical missense mutation is present in both the foveolar epithelium and oxyntic glands. Missense mutations are indicated by arrowheads. GNAS was sequenced using reverse primers.
Mentions: Sequencing analyses identified activating GNAS mutations in 27 GFM lesions (41%), 23 GH lesions (28%), and 5 adenocarcinomas (17% Table 2, Figure 2A). Activating KRAS mutations were found in 17 GFM lesions (26%), 2 GH lesions (2%), and 11 adenocarcinomas (37%). An activating BRAF mutation was found only in one GFM lesion (2%). None of the normal duodenal mucosa specimens showed any genetic alterations. Taken together, 36 GFM lesions (55%), 23 GH lesions (28%), and 15 adenocarcinomas (50%) harboured at least one of these genetic alterations (Table 3). Multiple independent lesions of GFM or GH were analysed in 10 patients. Among them, the mutational statuses of the lesions were discordant in six patients, confirming the multifocality of these lesions (Table 4).

Bottom Line: The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%).A BRAF mutation was found in only one GFM lesion (2%).A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations.

View Article: PubMed Central - PubMed

Affiliation: Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo 104-0045, Japan.

ABSTRACT

Background: Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds.

Methods: We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS, KRAS, and BRAF mutations.

Results: Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS-mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation.

Conclusions: A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours.

Show MeSH
Related in: MedlinePlus