ArticleGenome biology2021
Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 108 citations in OpenAlex.
- Review
- The Role of Alternative Splicing in Lung Cancer: Mechanisms, Regulators, and Therapeutic Implications.International journal of molecular sciences · 2026Review
- LINE-1 Epigenetic Repression and Regulation of Immunity.Viruses · 2026Review
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- The identification of RNA splicing aberrations and their potential regulatory network in Chinese non-small cell lung cancer.Respiratory research · 2026Article
- CoREST complex inhibition alters RNA splicing to promote neoantigen expression and enhance tumor immunity.JCI insight · 2026Article
- Predominant mutated non-canonical tumor-specific antigens identified by proteogenomics demonstrate immunogenicity and tumor suppression in CRC.Cell genomics · 2026Article
- Long-Read Sequencing Reveals RNA Splicing Complexity in Human Diseases.Computational and structural biotechnology journal · 2026Review
- Alternative Splicing-Mediated Resistance to Antibody-Based Therapies: Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- G-quadruplex structures as modulators of alternative promoter usage.NAR genomics and bioinformatics · 2025Article
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- Neoantigen-Driven Immunotherapy in Triple-Negative Breast Cancer: Emerging Strategies and Clinical Potential.Biomedicines · 2025Review
- Intron retention regulates STAT2 function and predicts immunotherapy response in lung cancer.bioRxiv : the preprint server for biology · 2025Article
- Of Context, Quality, and Complexity: Fine-Combing Tumor Mutational Burden in Immunotherapy-Treated Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Computation strategies and clinical applications in neoantigen discovery towards precision cancer immunotherapy.Biomarker research · 2025Review
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences.Oncogene · 2025Article
- Long-read RNA sequencing enables full-length chimeric transcript annotation of transposable elements in lung adenocarcinoma.BMC cancer · 2025Article
- Long-read RNA sequencing: A transformative technology for exploring transcriptome complexity in human diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape.eLife · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLong-read sequencing of full-length cDNAs enables the detection of structures of aberrant splicing isoforms in cancer cells. These isoforms are occasionally translated, presented by HLA molecules, and recognized as neoantigens. This study used a long-read sequencer (MinION) to construct a comprehensive catalog of aberrant splicing isoforms in non-small-cell lung cancers, by which novel isoforms and potential neoantigens are identified.
resultsFull-length cDNA sequencing is performed using 22 cell lines, and a total of 2021 novel splicing isoforms are identified. The protein expression of some of these isoforms is then validated by proteome analysis. Ablations of a nonsense-mediated mRNA decay (NMD) factor, UPF1, and a splicing factor, SF3B1, are found to increase the proportion of aberrant transcripts. NetMHC evaluation of the binding affinities to each type of HLA molecule reveals that some of the isoforms potentially generate neoantigen candidates. We also identify aberrant splicing isoforms in seven non-small-cell lung cancer specimens. An enzyme-linked immune absorbent spot assay indicates that approximately half the peptide candidates have the potential to activate T cell responses through their interaction with HLA molecules. Finally, we estimate the number of isoforms in The Cancer Genome Atlas (TCGA) datasets by referring to the constructed catalog and found that disruption of NMD factors is significantly correlated with the number of splicing isoforms found in the TCGA-Lung Adenocarcinoma data collection.
conclusionsOur results indicate that long-read sequencing of full-length cDNAs is essential for the precise identification of aberrant transcript structures in cancer cells.
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