ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Tumor-specific isoform switch of the fibroblast growth factor receptor 2 underlies the mesenchymal and malignant phenotypes of clear cell renal cell carcinomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure.Journal of the American Society of Nephrology : JASN · 2015Pooled it
- The Role of Alternative Splicing in Lung Cancer: Mechanisms, Regulators, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- The role of ESRP1 in solid tumor development through the regulation of CD44 splicing and EMT processes.Frontiers in oncology · 2025Review
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- Immunomodulatory Gene-Splicing Dysregulation in Tumorigenesis: Unmasking the Complexity.Molecules (Basel, Switzerland) · 2023Review
- CanIsoNet: a database to study the functional impact of isoform switching events in diseases.Bioinformatics advances · 2023Article
- Spatial expression of the FGFR2b splice isoform and its prognostic significance in endometrioid endometrial carcinoma.The journal of pathology. Clinical research · 2022Article
- [Expression and significance of fibroblast growth factor receptor 2 in clear cell renal cell carcinoma].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2022Article
- A repositioning screen using an FGFR2 splicing reporter reveals compounds that regulate epithelial-mesenchymal transitions and inhibit growth of prostate cancer xenografts.Molecular therapy. Methods & clinical development · 2022Article
- METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination.Molecular therapy. Nucleic acids · 2022Article
- Alternative RNA splicing in tumour heterogeneity, plasticity and therapy.Disease models & mechanisms · 2022Review
- Abnormal GRHL2 Methylation Confers Malignant Progression to Acute Leukemia.Applied bionics and biomechanics · 2022Article
- Alternative RNA splicing in stem cells and cancer stem cells: Importance of transcript-based expression analysis.World journal of stem cells · 2021Review
- Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?Cancers · 2021Article
- Alternative splicing modulates cancer aggressiveness: role in EMT/metastasis and chemoresistance.Molecular biology reports · 2021Review
- 2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.Journal of oncology · 2021Review
- Deletion ofDisease models & mechanisms · 2020Article
- Role of PKCε in the epithelial-mesenchymal transition induced by FGFR2 isoform switch.Cell communication and signaling : CCS · 2020Article
- The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing.Nature communications · 2020Article
- Genome-wide Analysis of the Alternative Splicing Profiles Revealed Novel Prognostic Index for Kidney Renal Cell Clear Cell Carcinoma.Journal of Cancer · 2020Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeWe aim to identify tumor-specific alternative splicing events having potential applications in the early detection, diagnosis, prognosis, and therapy for cancers. EXPERIMENTAL
designWe analyzed RNA-seq data on 470 clear cell renal cell carcinomas (ccRCC) and 68 kidney tissues to identify tumor-specific alternative splicing events. We further focused on the fibroblast growth factor receptor 2 (FGFR2) isoform switch and characterized ccRCCs expressing different FGFR2 isoforms by integrated analyses using genomic data from multiple platforms and tumor types.
resultsWe identified 113 top candidate alternatively spliced genes in ccRCC. Prominently, the FGFR2 gene transcript switched from the normal IIIb isoform ("epithelial") to IIIc isoform ("mesenchymal") in nearly 90% of ccRCCs. This switch is kidney specific as it was rarely observed in other cancers. The FGFR2-IIIb ccRCCs show a transcriptome and methylome resembling those from normal kidney, whereas FGFR2-IIIc ccRCCs possess elevated hypoxic and mesenchymal expression signatures. Clinically, FGFR2-IIIb ccRCCs are smaller in size, of lower tumor grade, and associated with longer patient survival. Gene set enrichment and DNA copy number analyses indicated that FGFR2-IIIb ccRCCs are closely associated with renal oncocytomas and chromophobe RCCs (chRCC). A reexamination of tumor histology by pathologists identified FGFR2-IIIb tumors as chRCCs and clear cell papillary RCCs (ccpRCC).
conclusionsFGFR2 IIIb RCCs represent misdiagnosed ccRCC cases, suggesting FGFR2 isoform testing can be used in the diagnosis of RCC subtypes. The finding of a prevalent isoform switch of FGFR2 in a tissue-specific manner holds promise for the future development of FGFR2-IIIc as a distinct early detection biomarker and therapeutic target for ccRCC.
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