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  • Perspective
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OPINION

Clinical potential of mass spectrometry-based proteogenomics

Nature Reviews Clinical Oncology volume 16, pages 256–268 (2019)Cite this article

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Abstract

Cancer genomics research aims to advance personalized oncology by finding and targeting specific genetic alterations associated with cancers. In genome-driven oncology, treatments are selected for individual patients on the basis of the findings of tumour genome sequencing. This personalized approach has prolonged the survival of subsets of patients with cancer. However, many patients do not respond to the predicted therapies based on the genomic profiles of their tumours. Furthermore, studies pairing genomic and proteomic analyses of samples from the same tumours have shown that the proteome contains novel information that cannot be discerned through genomic analysis alone. This observation has led to the concept of proteogenomics, in which both types of data are leveraged for a more complete view of tumour biology that might enable patients to be more successfully matched to effective treatments than they would using genomics alone. In this Perspective, we discuss the added value of proteogenomics over the current genome-driven approach to the clinical characterization of cancers and summarize current efforts to incorporate targeted proteomic measurements based on selected/multiple reaction monitoring (SRM/MRM) mass spectrometry into the clinical laboratory to facilitate clinical proteogenomics.

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Fig. 1: Many processes downstream of the genome can affect the tumour phenotype.
Fig. 2: Untargeted (‘shotgun’) discovery proteomics.
Fig. 3: Integrative proteogenomic analysis adds missing biology.
Fig. 4: Targeted MS-based assays.

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Acknowledgements

The work of the authors is supported by the US Department of Health & Human Services, the US National Institutes of Health (NIH) and US National Cancer Institute grants U01 CA214114 (A.G.P. and A.N.H.), R50 CA211499 (J.R.W.), U01 CA214116 (K.D.R) and U24 CA210954 (B.Z.).

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Authors and Affiliations

  1. Department of Molecular and Human Genetics, Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA

    Bing Zhang

  2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Jeffrey R. Whiteaker & Amanda G. Paulovich

  3. Department of Medicine, University of Washington, Seattle, WA, USA

    Andrew N. Hoofnagle

  4. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

    Andrew N. Hoofnagle & Geoffrey S. Baird

  5. Department of Pathology, University of Washington, Seattle, WA, USA

    Geoffrey S. Baird

  6. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA

    Karin D. Rodland

  7. Department of Cell, Development and Cancer Biology, Oregon Health & Sciences University, Portland, OR, USA

    Karin D. Rodland

  8. Division of Medical Oncology, University of Washington School of Medicine, Seattle, WA, USA

    Amanda G. Paulovich

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  1. Bing Zhang
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All authors made substantial contributions to all aspects of the preparation of this manuscript.

Corresponding author

Correspondence to Amanda G. Paulovich.

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Competing interests

A.N.H. receives grant funding and instrument support from Waters, Inc. G.S.B. is a consultant for Avalon Healthcare Solutions. A.G.P. receives instrument support from Sciex and is the founder of Precision Assays. B.Z., J.R.W., G.S.B. and K.D.R. declare no competing interests.

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Zhang, B., Whiteaker, J.R., Hoofnagle, A.N. et al. Clinical potential of mass spectrometry-based proteogenomics. Nat Rev Clin Oncol 16, 256–268 (2019). https://doi.org/10.1038/s41571-018-0135-7

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