ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Comprehensive Analysis of R-Spondin Fusions and RNF43 Mutations Implicate Novel Therapeutic Options in Colorectal Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
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- Clinicopathologic, genetic and immune cell infiltration analysis of colorectal signet ring cell carcinoma with comparison to conventional adenocarcinoma.Journal of the National Cancer Center · 2026Article
- Oncofetal reprogramming and cellular plasticity in colorectal cancer: from mechanisms to clinical translation.Frontiers in oncology · 2026Review
- RSPO4 exerts tumor suppression through antagonizing canonical and non-canonical Wnt signaling.International journal of biological sciences · 2026Article
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- Single-Cell Transcriptomics Reveals Cellular Heterogeneity and Drivers in Serrated Pathway-Driven Colorectal Cancer Progression.International journal of molecular sciences · 2024Article
- CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways.Diseases (Basel, Switzerland) · 2024Article
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- Protein and mRNA Expression in Uveal Melanoma Cell Lines Are Related to GNA and BAP1 Mutation Status.Investigative ophthalmology & visual science · 2024Article
- Recurrent mutations in tumor suppressorScience advances · 2024Article
- Clinical and molecular characteristics ofTherapeutic advances in medical oncology · 2024Article
- Navigating through novelties concerning mCRC treatment-the role of immunotherapy, chemotherapy, and targeted therapy in mCRC.Frontiers in surgery · 2024Review
- R-spondin family biology and emerging linkages to cancer.Annals of medicine · 2023Review
- Pan-cancer analysis identifies RNF43 as a prognostic, therapeutic and immunological biomarker.European journal of medical research · 2023Article
- Comprehensive genomic characterization of sporadic synchronous colorectal cancer: Implications for treatment optimization and clinical outcome.Cell reports. Medicine · 2023Article
- Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.Current pharmacology reports · 2023Article
Corrections and comments
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Authors and funding
28 authors at 12 institutions in 5 countries.
Funding
Abstract
purposeGene fusions involving R-spondin (RSPOfp) and RNF43 mutations have been shown to drive Wnt-dependent tumor initiation in colorectal cancer. Herein, we aimed to characterize the molecular features of RSPOfp/RNF43 mutated (mut) compared with wild-type (WT) colorectal cancers to gain insights into potential rationales for therapeutic strategies. EXPERIMENTAL
designA discovery cohort was classified for RSPOfp/RNF43 status using DNA/RNA sequencing and IHC. An independent cohort was used to validate our findings.
resultsThe discovery cohort consisted of 7,245 colorectal cancer samples. RSPOfp and RNF43 mutations were detected in 1.3% (n = 94) and 6.1% (n = 443) of cases. We found 5 RSPO fusion events that had not previously been reported (e.g., IFNGR1-RSPO3). RNF43-mut tumors were associated with right-sided primary tumors. No RSPOfp tumors had RNF43 mutations. In comparison with WT colorectal cancers, RSPOfp tumors were characterized by a higher frequency of BRAF, BMPR1A, and SMAD4 mutations. APC mutations were observed in only a minority of RSPOfp-positive compared with WT cases (4.4% vs. 81.4%). Regarding RNF43 mutations, a higher rate of KMT2D and BRAF mutations were detectable compared with WT samples. Although RNF43 mutations were associated with a microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) phenotype (64.3%), and a tumor mutation burden ≥10 mt/Mb (65.8%), RSPOfp was not associated with MSI-H/dMMR. The validation cohort replicated our genetic findings.
conclusionsThis is the largest series of RSPOfp/RNF43-mut colorectal cancers reported to date. Comprehensive molecular analyses asserted the unique molecular landscape associated with RSPO/RNF43 and suggested potential alternative strategies to overcome the low clinical impact of Wnt-targeted agents and immunotherapy.
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