Evidence for heightened genetic instability in precancerous spasmolytic polypeptide expressing gastric glands.
J Med Genet
; 57(6): 385-388, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-30877236
ABSTRACT
BACKGROUND:
Spasmolytic polypeptide-expressing metaplasia (SPEM) is present in more than 90% of resected gastric cancer tissues. However, although widely regarded as a pre-cancerous tissue, its genetic characteristics have not been well studied.METHODS:
Immunohistochemistry using Trefoil factor 2 (TFF2) antibodies was used to identify TFF2-positive SPEM cells within SPEM glands in the stomach of Helicobacter felis (H. felis) -infected mice and human clinical samples. Laser microdissection was used to isolate specific cells from both the infected mice and the human samples. The genetic instability in these cells was examined by measuring the lengths of microsatellite (MS) markers using capillary electrophoresis. Also, genome-wide genetic variations in the SPEM cells from the clinical sample was examined using deep whole-exome sequencing.RESULTS:
SPEM cells indeed exhibit not only heightened MS instability (MSI), but also genetic instabilities that extend genome-wide. Furthermore, surprisingly, we found that morphologically normal, TFF2-negative cells also contain a comparable degree of genomic instabilities as the co-resident SPEM cells within the SPEM glands.CONCLUSION:
These results, for the first time, clearly establish elevated genetic instability as a critical property of SPEM glands, which may provide a greater possibility for malignant clone selection. More importantly, these results indicate that SPEM cells may not be the sole origin of carcinogenesis in the stomach and strongly suggest the common progenitor of these cells, the stem cells, as the source of these genetic instabilities, and thus, potential key players in carcinogenesis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Peptídeos e Proteínas de Sinalização Intercelular
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Fator Trefoil-2
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Metaplasia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China