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Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification

Author

Listed:
  • Celina Tretter

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Niklas Andrade Krätzig

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IInd Medical Department
    Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM)
    Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics)

  • Matteo Pecoraro

    (Max Plank Institute of Biochemistry
    Università della Svizzera italiana)

  • Sebastian Lange

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IInd Medical Department
    Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM)
    Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics)

  • Philipp Seifert

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Clara Frankenberg

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Johannes Untch

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Gabriela Zuleger

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Mathias Wilhelm

    (Technical University of Munich, TUM School of Life Sciences, Chair of Proteomics and Bioanalytics
    Technical University of Munich, TUM School of Life Sciences, Computational Mass Spectrometry)

  • Daniel P. Zolg

    (Technical University of Munich, TUM School of Life Sciences, Chair of Proteomics and Bioanalytics)

  • Florian S. Dreyer

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Eva Bräunlein

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Thomas Engleitner

    (Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM)
    Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics)

  • Sebastian Uhrig

    (German Cancer Consortium (DKTK), partner site Heidelberg and German Cancer Research Center (DKFZ)
    Molecular Precision Oncology Program, NCT Heidelberg)

  • Melanie Boxberg

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology)

  • Katja Steiger

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology)

  • Julia Slotta-Huspenina

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology)

  • Sebastian Ochsenreither

    (German Cancer Consortium (DKTK), partner site Berlin and German Cancer Research Center (DKFZ)
    Charité – Universitätsmedizin Berlin
    Charité – Universitätsmedizin Berlin)

  • Nikolas Bubnoff

    (German Cancer Consortium (DKTK), partner site Freiburg and German Cancer Research Center (DKFZ)
    University of Freiburg
    University of Schleswig Holstein, Campus Lübeck)

  • Sebastian Bauer

    (German Cancer Consortium (DKTK), partner site Essen and German Cancer Research Center (DKFZ)
    University Hospital Essen)

  • Melanie Boerries

    (German Cancer Consortium (DKTK), partner site Freiburg and German Cancer Research Center (DKFZ)
    University of Freiburg)

  • Philipp J. Jost

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department
    Medical University of Graz
    University Comprehensive Cancer Center Graz, Medical University of Graz)

  • Kristina Schenck

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Iska Dresing

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Florian Bassermann

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department
    Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM))

  • Helmut Friess

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Department of Surgery)

  • Daniel Reim

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Department of Surgery)

  • Konrad Grützmann

    (German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ)
    Core Unit Molecular Tumor Diagnostics (CMTD), NCT Dresden
    Faculty of Medicine, TU Dresden)

  • Katrin Pfütze

    (German Cancer Consortium (DKTK), partner site Heidelberg and German Cancer Research Center (DKFZ))

  • Barbara Klink

    (German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ)
    Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden)

  • Evelin Schröck

    (German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ)
    Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden
    ERN GENTURIS, Hereditary Cancer Syndrome Center Dresden
    National Center for Tumor Diseases Dresden (NCT/UCC))

  • Bernhard Haller

    (Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of AI and Informatics in Medicine)

  • Bernhard Kuster

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Life Sciences, Chair of Proteomics and Bioanalytics
    Technical University of Munich, TUM School of Life Sciences, Bavarian Biomolecular Mass Spectrometry Center (BayBioMS))

  • Matthias Mann

    (Max Plank Institute of Biochemistry)

  • Wilko Weichert

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology)

  • Stefan Fröhling

    (German Cancer Consortium (DKTK), partner site Heidelberg and German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ))

  • Roland Rad

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IInd Medical Department
    Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM)
    Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics)

  • Michael Hiltensperger

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department)

  • Angela M. Krackhardt

    (German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ)
    Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department
    Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM)
    Malteser Krankenhaus St. Franziskus-Hospital)

Abstract

Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.

Suggested Citation

  • Celina Tretter & Niklas Andrade Krätzig & Matteo Pecoraro & Sebastian Lange & Philipp Seifert & Clara Frankenberg & Johannes Untch & Gabriela Zuleger & Mathias Wilhelm & Daniel P. Zolg & Florian S. Dr, 2023. "Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39570-7
    DOI: 10.1038/s41467-023-39570-7
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