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Transcriptomic profiling of signet ring cell precursors of diffuse-type gastric cancer informs latent phenotype

ABSTRACT: Germline CDH1 loss-of-function mutations are causally linked to an increased lifetime risk of diffuse gastric cancer (DGC). Early, multifocal signet ring cell (SRC) lesions are ubiquitous among CDH1 variant carriers, yet only a subset of patients will develop advanced DGC. Transcriptomic profiling was performed to establish the molecular phenotype of early SRC lesions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281274 | GEO | 2025/02/21

REPOSITORIES: GEO

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Spatial transcriptomic profiling of signet ring cell precursors of diffuse-type gastric cancer

Project description:Germline CDH1 loss-of-function mutations are causally linked to an increased lifetime risk of diffuse gastric cancer (DGC). Early, multifocal signet ring cell (SRC) lesions are ubiquitous among CDH1 variant carriers, yet only a subset of patients will develop advanced DGC. Transcriptomic profiling was performed to establish the molecular phenotype of early SRC lesions.

2025-02-21 | GSE289923 | GEO

Transcriptomic changes in signet ring cell colorectal cancer

Project description:Data used to look for gene expression changes correlating with DNA methylation in signet ring cell colorectal cancer.

2017-07-21 | GSE79793 | GEO

DNA methylation profiling of signet ring cell colorectal cancer

Project description:Identification of molecular subtypes of colorectal signet ring cell carcinoma based on differences in DNA methylation.

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Dual roles of ARID1A in both mucin production and secretion to restrain gastric signet ring cell carcinoma [ATAC-Seq]

Project description:Signet ring cell carcinoma (SRCC) of the stomach is a subtype of gastric cancer with poor prognosis. It is characterized with unique large vacuoles of mucin and compressed nucleus, which resemble signet rings, while the underlying molecular mechanisms driving SRCC remain elusive. Here, we studied whether and how human gastric SRCC-associated ARID1A deficiency drove the disease.

2024-09-18 | GSE232291 | GEO

Dual roles of ARID1A in both mucin production and secretion to restrain gastric signet ring cell carcinoma [Cut & Tag]

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Dual roles of ARID1A in both mucin production and secretion to restrain gastric signet ring cell carcinoma [RNA-Seq]

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Comparison of gene expression profile between Well differentiated Adenocarcinoma and Signet Ring Cell Carcinoma in Colorectal cancer

Project description:This experiment was performed to compare and intend to acquire a genetic expression feature of signet ring cell carcinoma in colorectal cancer that is extremely rare histological type and also shows significantly worse prognosis compared with conventional histological type of the cancer.

2021-05-23 | E-MTAB-9149 | biostudies-arrayexpress

Synergistic Tumor Suppressor Activity of E-cadherin and p53 in a Conditional Mouse Model for Diffuse-Type Gastric Cancer

Project description:BACKGROUND & AIMS: Gastric cancer is the second most frequent cause of death from cancer in the world, diffuse-type gastric cancer (DGC) exhibiting a poor prognosis. Germline mutations of CDH1, encoding E-cadherin, have been reported in hereditary DGCs, and genetic and/or epigenetic alterations of CDH1 are frequently detected in sporadic DGCs. Genetic alterations of TP53 are also frequently found in DGCs. To examine the synergistic effect of loss of E-cadherin and p53 on gastric carcinogenesis, we established a mouse line in which E-cadherin and p53 are specifically inactivated in the stomach parietal cell lineage. METHODS: We crossed Atp4b-Cre mice with Cdh1loxP/loxP and Trp53loxP/loxP mice, and examined the gastric phenotype of Atp4b-Cre+;Cdh1loxP/loxP;Trp53loxP/loxP mice. RESULTS: Non-polarization of E-cadherin-negative parietal cells and proton pump-negative atypical foci were observed in the transgenic mice. Intramucosal cancers and invasive cancers composed of poorly differentiated carcinoma cells and signet ring cells, which were histologically very similar to those in humans, were found from 6 and 9 months, respectively. Fatal DGCs developed at 100% penetrance within a year, frequently metastasized to lymph nodes, and had tumorigenic activity in immunodeficient mice. Gene expression profiling analyses also revealed that DGCs in the E-cadherin/p53-deficient mice resembled human DGCs. CONCLUSIONS: Our mouse line is the first genetically modified mouse model of DGC and very useful for clarifying the mechanism underlying gastric carcinogenesis, and provides a new approach to the treatment and prevention of DGC because of morphological and biochemical similarities with human DGC. Two-condition experiment, Gastric cancer vs. normal gastric mucosal tissues. Biological replicates: pooled control sample from five normal gastric mucosal tissues, three replicates from diffuse-type gastric cancer.

2011-12-04 | E-GEOD-25302 | biostudies-arrayexpress

Synergistic Tumor Suppressor Activity of E-cadherin and p53 in a Conditional Mouse Model for Diffuse-Type Gastric Cancer

2011-12-04 | GSE25302 | GEO

Inherited KDM6AA649T facilitates tumor-immune escape and exacerbates colorectal signet-ring cell carcinoma outcomes

Project description:Childhood onset of colorectal signet ring cell carcinoma (CR-SRCC) is extremely rare and featured as highly malignant with poor prognosis. Here we reported a CR-SRCC case of 11-year-old boy with a novel inherited X-linked KDM6AA694T mutation. The H3K27me2/3 demethylase KDM6A was frequently mutated in varieties of tumors and acts as a tumor suppressor. In vivo H3K27me3 demethylation assay demonstrated that KDM6AA694T had dampened H3K27me3 demethylase activity. Overexpression of KDM6AA694T in SRCC cell line KATO3 promoted cell proliferation, invasion and migration, which were further confirmed in vivo by constructing orthotopic tumor growth and lung metastasis model. Besides, expression of KDM6AA694T in immune cells suppresses inflammatory macrophage response and effector T cell response. In conclusion, we characterized a novel inherited KDM6AA694T mutant from a childhood-onset SRCC case and demonstrated that the mutant with impaired H3K27me3 demethylase activity could potentiate tumor malignancy and suppress antitumor immunity.

2025-01-25 | GSE253804 | GEO

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