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Genome Editing: A Tool For Research and Therapy: Towards a functional understanding of variants for molecular diagnostics using genome editing

Nature Medicine volume 20, pages 1103–1104 (2014)Cite this article

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Continued advancement of next-generation DNA sequencing methods promises to make low-cost, rapid genome sequencing of patient samples a reality in the near future. The value of genetic information has been well established in cancer, both for diagnosis and for predicting response to therapy, and will also have substantial impacts on clinical decision making for a wide variety of diseases. However, an important challenge that molecular pathologists face is the interpretation of so-called sequence variants of unknown significance. For example, clinical sequencing of tumor-related genes can yield many sequence variants whose functional importance is not defined by databases that catalog disease-relevant mutations such as COSMIC1. Furthermore, current in silico predictors of function have limitations (for example, those from algorithms such as SIFT2 and PolyPhen-2 (ref. 3)), and genetic association studies alone are insufficient to precisely identify disease causal variation4.

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Authors and Affiliations

  1. A. John Iafrate and J. Keith Joung are at the Department of Pathology, Shengdar Q. Tsai, Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.,

    Shengdar Q Tsai, A John Iafrate & J Keith Joung

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  1. Shengdar Q Tsai
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  2. A John Iafrate
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  3. J Keith Joung
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Correspondence to J Keith Joung.

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Competing interests

J.K.J. is a consultant for Horizon Discovery. J.K.J. has financial interests in Editas Medicine and Transposagen Biopharmaceuticals. J.K.J.'s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies.

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Tsai, S., Iafrate, A. & Joung, J. Genome Editing: A Tool For Research and Therapy: Towards a functional understanding of variants for molecular diagnostics using genome editing. Nat Med 20, 1103–1104 (2014). https://doi.org/10.1038/nm.3722

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