ArticleBlood2020
Rare and private spliceosomal gene mutations drive partial, complete, and dual phenocopies of hotspot alterations.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 16 citations in OpenAlex.
- Sensitivity to ATR-CHK1 pathway inhibition in MDS/AML is enhanced by SRSF2 mutations and reduced by RUNX1 loss.Leukemia · 2026Article
- U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations.Nature genetics · 2026Article
- U2af1Leukemia · 2026Article
- Variant-specific SF3B1 mutations drive distinct splicing and mitochondrial dysfunction in myelodysplastic neoplasms.Human genomics · 2026Article
- Critical Role of Molecular-Based Stratification in Low-Risk Myelodysplastic Syndrome with Direct Progression to Acute Myeloid Leukemia: A Case Report.International journal of molecular sciences · 2026Article
- Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators.Science advances · 2026Article
- Splicing Factor Mutations in Chronic Myelomonocytic Leukemia: Biological Consequences and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations.bioRxiv : the preprint server for biology · 2025Article
- Molecular impact of mutations in RNA splicing factors in cancer.Molecular cell · 2024Review
- The E592K variant of SF3B1 creates unique RNA missplicing and associates with high-risk MDS without ring sideroblasts.Blood advances · 2024Article
- Biological relevance of alternative splicing in hematologic malignancies.Molecular medicine (Cambridge, Mass.) · 2024Review
- SRSF2 plays an unexpected role as reader of mMolecular cell · 2023Article
- SF3B1 mutations in myelodysplastic syndromes: A potential therapeutic target for modulating the entire disease process.Frontiers in oncology · 2023Review
- Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells.Nature biotechnology · 2022Article
- Genome-wide screening identifies cell-cycle control as a synthetic lethal pathway with SRSF2P95H mutation.Blood advances · 2022Article
- Article
- RNA-binding proteins of COSMIC importance in cancer.The Journal of clinical investigation · 2021Review
- Aberrant Alternative Splicing in U2af1/Tet2 Double Mutant Mice Contributes to Major Hematological Phenotypes.International journal of molecular sciences · 2021Article
- Interpreting Sequence Variation in PDAC-Predisposing Genes Using a Multi-Tier Annotation Approach Performed at the Gene, Patient, and Cohort Level.Frontiers in oncology · 2021Article
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9 authors at 4 institutions in 2 countries.
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Abstract
Genes encoding the RNA splicing factors SF3B1, SRSF2, and U2AF1 are subject to frequent missense mutations in clonal hematopoiesis and diverse neoplastic diseases. Most "spliceosomal" mutations affect specific hotspot residues, resulting in splicing changes that promote disease pathophysiology. However, a subset of patients carries spliceosomal mutations that affect non-hotspot residues, whose potential functional contributions to disease are unstudied. Here, we undertook a systematic characterization of diverse rare and private spliceosomal mutations to infer their likely disease relevance. We used isogenic cell lines and primary patient materials to discover that 11 of 14 studied rare and private mutations in SRSF2 and U2AF1 induced distinct splicing alterations, including partially or completely phenocopying the alterations in exon and splice site recognition induced by hotspot mutations or driving "dual" phenocopies that mimicked 2 co-occurring hotspot mutations. Our data suggest that many rare and private spliceosomal mutations contribute to disease pathogenesis and illustrate the utility of molecular assays to inform precision medicine by inferring the potential disease relevance of newly discovered mutations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.