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Precision oncology in the age of integrative genomics

Abstract

Precision oncology applies genomic and other molecular analyses of tumor biopsies to improve the diagnosis and treatment of cancers. In addition to identifying therapeutic options, precision oncology tracks the response of a tumor to an intervention at the molecular level and detects drug resistance and the mechanisms by which it occurs. Integrative genomics can include sequencing specific panels of genes, exomes, or the entire triad of the patient's germline, tumor exome, and tumor transcriptome. Although the capabilities of sequencing technologies continue to improve, widespread adoption of genomics-driven precision oncology in the clinic has been held back by logistical, regulatory, financial, and ethical considerations. Nevertheless, integrative clinical sequencing programs applied at the point of care have the potential to improve the clinical management of cancer patients.

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Figure 1: The progression of analytical tools in oncology.
Figure 2: Integrative sequencing analysis to define the spectrum of cancer aberrations.
Figure 3: Workflow of integrative clinical sequencing for precision oncology.

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Acknowledgements

This work was supported in part by the NIH Early Detection Research Network Award U01 CA214170, the NIH Clinical Sequencing Exploratory Research (CSER) Award NIH 1UM1HG006508, a Prostate SPORE Award P50 CA186786, and awards from the Prostate Cancer Foundation. A.M.C. is an American Cancer Society Research Professor, a Howard Hughes Medical Institute Investigator, and a Taubman Scholar of the University of Michigan. We thank S. Ellison, scientific writer, for editorial help with the manuscript and R. Kunkel for figure artwork. Helpful discussions with the members of the MI_Oncoseq team including D. Robinson, R. Lonigro, M. Cieslik, Y.-M. Wu, S.M. Dhanasekaran, P. Vats, and X. Cao are gratefully acknowledged.

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Correspondence to Chandan Kumar-Sinha or Arul M Chinnaiyan.

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A.M.C. currently serves on the scientific advisory board of Tempus.

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Supplementary Table 1

Summary of actionable germline aberrations in cancer predisposition genes (XLSX 20 kb)

Supplementary Table 2a and 2b

A. Germline aberrations currently in clinical trials. Summary of actionable somatic aberrations in cancer genes. (XLSX 34 kb)

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Kumar-Sinha, C., Chinnaiyan, A. Precision oncology in the age of integrative genomics. Nat Biotechnol 36, 46–60 (2018). https://doi.org/10.1038/nbt.4017

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