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Personal regulome navigation of cancer

Nature Reviews Cancer volume 21, pages 609–610 (2021)Cite this article

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A systematic approach to understanding the noncoding genome in cancer promises to improve cancer diagnosis and therapy. Tracking the landscape of gene control in individual patients and single cells yields many insights for inherited and somatic mutations in cancer, extrachromosomal oncogene amplifications and cancer immunotherapy. New technologies and bold therapeutic approaches are paving the way to truly envisage personalized cancer medicine in the future.

The era of the personal genome has arrived, but the dream of precision medicine enabled by a personalized understanding of disease etiology and dynamic response to treatment is only now starting to be realized. Cancer is a disease of genes, and much of cancer genetics has focused on coding mutations that alter protein sequence. By contrast, unbiased genome-wide association studies, including for cancer predisposition, showed that the vast majority of inherited variants associated with human disease are located tens of thousands of bases away from genes, in the noncoding genome that comprise 98% of human DNA. A deep technological chasm existed between the knowledge from abundant cell sources in laboratory settings and our ability to infer regulatory landscapes of diseases from miniscule clinical samples in individual patients. Therefore, it has become clear that a personal genome is not sufficient for personalized medicine. Instead, a personalized regulome, enabled by interrogation of the regulatory landscape of personal disease, is required for informed interventions.

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Fig. 1: Layering insights from regulomes.

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Acknowledgements

Supported by NIH RM1-HG007735, R35-CA209919. H.Y.C. is an Investigator of the Howard Hughes Medical Institute.

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  1. Center for Personal Dynamic Regulomes and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA

    Howard Y. Chang

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  1. Howard Y. Chang
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Correspondence to Howard Y. Chang.

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Competing interests

H.Y.C. is a co-founder of Accent Therapeutics, Boundless Bio, and is an advisor of 10x Genomics, Arsenal Biosciences and Spring Discovery.

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Chang, H.Y. Personal regulome navigation of cancer. Nat Rev Cancer 21, 609–610 (2021). https://doi.org/10.1038/s41568-021-00381-x

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