ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
Indolent feature of Helicobacter pylori-uninfected intramucosal signet ring cell carcinomas with CDH1 mutations.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 30 citations in OpenAlex.
- Mapping the genetic landscape of hereditary diffuse-type gastric cancer progression.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Clinico-epidemiological Characteristics of Helicobacter pylori-naïve Undifferentiated Gastric Cancer.Internal medicine (Tokyo, Japan) · 2026Article
- <italic>Helicobacter pylori</italic>-Naïve Gastric Neoplasms: Clinicopathological and Molecular Features and Diagnostic Challenges.Digestion · 2026Review
- Gastric Epithelial Neoplasms in <italic>Helicobacter pylori</italic>-Uninfected Patients.Digestion · 2026Review
- The Changing Landscape of Hereditary Diffuse Gastric Cancer.Journal of gastric cancer · 2026Review
- Helicobacter pylori-naïve status is associated with poor prognosis and aggressive pathological features in undifferentiated-type gastric cancer: a multi-center retrospective cohort study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Transcriptional profiling revealsFrontiers in immunology · 2025Article
- A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Clinicopathological and endoscopic features of Helicobacter pylori infection-negative gastric cancer in Japan: a retrospective study.Clinical endoscopy · 2024Article
- Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis.Journal of gastroenterology · 2024Article
- Exploring quality indicators for the detection of Helicobacter pylori-naïve gastric cancer: a cross-sectional nationwide survey.Clinical endoscopy · 2023Article
- [Clinicopathological features ofBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2023Article
- Genomic features of Helicobacter pylori-naïve diffuse-type gastric cancer.The Journal of pathology · 2022Article
- Clinicopathological and molecular characterization of early gastric adenocarcinoma in Helicobacter pylori-uninfected patients: emphasis on differentiated gastric adenocarcinoma.Journal of gastroenterology · 2022Article
- Helicobacter pylori promotes gastric cancer progression through the tumor microenvironment.Applied microbiology and biotechnology · 2022Review
- Do Gastric Signet Ring Cell Carcinomas and ECL-Cell Neuroendocrine Tumours Have a Common Origin?Medicina (Kaunas, Lithuania) · 2022Article
- Author's reply to the letter to the editor on "A case of gastric signet-ring cell carcinoma with a long-term retrospective follow-up of 17 years".Clinical journal of gastroenterology · 2022Article
- Intramucosal signet-ring cell carcinoma with reduced expression of E-cadherin in a Helicobacter pylori-uninfected stomach remained unchanged for 8 years.Clinical journal of gastroenterology · 2022Article
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn Helicobacter pylori (Hp)-uninfected individuals, diffuse-type gastric cancer (DGC) was reported as the most common type of cancer. However, the carcinogenic mechanism of Hp-uninfected sporadic DGC is largely unknown.
methodsWe performed whole-exome sequencing of Hp-uninfected DGCs and Hp-uninfected normal gastric mucosa. For advanced DGCs, external datasets were also analyzed.
resultsEighteen patients (aged 29-78 years) with DGCs and nine normal subjects (28-77 years) were examined. The mutation burden in intramucosal DGCs (10-66 mutations per exome) from individuals aged 29-73 years was not very different from that in the normal gastric glands, which showed a constant mutation accumulation rate (0.33 mutations/exome/year). Unbiased dN/dS analysis showed that CDH1 somatic mutation was a driver mutation for intramucosal DGC. CDH1 mutation was more frequent in intramucosal DGCs (67%) than in advanced DGCs (27%). In contrast, TP53 mutation was more frequent in advanced DGCs (52%) than in intramucosal DGCs (0%). This discrepancy in mutations suggests that CDH1-mutated intramucosal DGCs make a relatively small contribution to advanced DGC formation. Among the 16 intramucosal DGCs (median size, 6.5 mm), 15 DGCs were pure signet ring cell carcinoma (SRCC) with reduced E-cadherin expression and a low proliferative capacity (median Ki-67 index, 2.4%). Five SRCCs reviewed endoscopically over 2-5 years showed no progression.
conclusionsImpaired E-cadherin function due to CDH1 mutation was considered as an early carcinogenic event of Hp-uninfected intramucosal SRCC. Genetic and clinical analyses suggest that Hp-uninfected intramucosal SRCCs may be less likely to develop into advanced DGCs.
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