ArticleGenome biology2014
Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine.Cellular oncology (Dordrecht, Netherlands) · 2025Pooled it
- 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
- Conditionally Reprogrammed Cells Preserve Cellular Diversity and Permit Genetic Manipulation: Implications for Cancer Heterogeneity and Tissue Regeneration.Serican journal of medicine · 2026Article
- Single-cell aneuploidy and chromosomal arm imbalances define subclones with divergent transcriptomic phenotypes.NAR genomics and bioinformatics · 2025Article
- Review
- Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation.Bioelectronic medicine · 2025Review
- Unveiling racial disparities in prostate cancer using an integrative genomic and transcriptomic analysis.Cell insight · 2025Article
- Individualized Pooled CRISPR/Cas9 Screenings Identify CDK2 as a Druggable Vulnerability in a Canine Mammary Carcinoma Patient.Veterinary sciences · 2025Article
- Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.Frontiers in cell and developmental biology · 2025Review
- Krukenberg tumours: which patients should be considered for surgery?-a narrative literature review.Translational cancer research · 2024Review
- Significance of dysregulated M2 macrophage andTranslational cancer research · 2024Article
- Review
- An Exploration of Organoid Technology: Present Advancements, Applications, and Obstacles.Current pharmaceutical biotechnology · 2024Review
- Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids.Oncogene · 2024Article
- Functional screening of amplification outlier oncogenes in organoid models of early tumorigenesis.Cell reports · 2023Article
- A new scaffold-free tumoroid model provides a robust preclinical tool to investigate invasion and drug response in Renal Cell Carcinoma.Cell death & disease · 2023Article
- Review
- 3D cancer models: One step closer toFrontiers in immunology · 2023Review
- Copy number alterations and epithelial‑mesenchymal transition genes in diffuse and intestinal gastric cancers in Mexican patients.Molecular medicine reports · 2022Article
- High-resolution positron emission microscopy of patient-derived tumor organoids.Nature communications · 2021Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundGastric cancer is the second-leading cause of global cancer deaths, with metastatic disease representing the primary cause of mortality. To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. This involves a comparison between a primary tumor from a hereditary diffuse gastric cancer syndrome proband and its recurrence as an ovarian metastasis.
resultsBoth the primary tumor and ovarian metastasis have common biallelic loss-of-function of both the CDH1 and TP53 tumor suppressors, indicating a common genetic origin. While the primary tumor exhibits amplification of the Fibroblast growth factor receptor 2 (FGFR2) gene, the metastasis notably lacks FGFR2 amplification but rather possesses unique biallelic alterations of Transforming growth factor-beta receptor 2 (TGFBR2), indicating the divergent in vivo evolution of a TGFBR2-mutant metastatic clonal population in this patient. As TGFBR2 mutations have not previously been functionally validated in gastric cancer, we modeled the metastatic potential of TGFBR2 loss in a murine three-dimensional primary gastric organoid culture. The Tgfbr2 shRNA knockdown within Cdh1-/-; Tp53-/- organoids generates invasion in vitro and robust metastatic tumorigenicity in vivo, confirming Tgfbr2 metastasis suppressor activity.
conclusionsWe document the metastatic differentiation and genetic heterogeneity of diffuse gastric cancer and reveal the potential metastatic role of TGFBR2 loss-of-function. In support of this study, we apply a murine primary organoid culture method capable of recapitulating in vivo metastatic gastric cancer. Overall, we describe an integrated approach to identify and functionally validate putative cancer drivers involved in metastasis.
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