Corresponding Author: Eliezer M. Van Allen, MD, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 360 Longwood Ave, LC9329, Boston, MA 02215 (eliezerm_vanallen@dfci.harvard.edu).
Accepted for Publication: October 6, 2020.
Author Contributions: Drs AlDubayan and Van Allen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: AlDubayan, Conway, Al-Rubaish, Al-Sulaiman, Al-Ali, Taylor-Weiner, Van Allen.
Acquisition, analysis, or interpretation of data: AlDubayan, Conway, Camp, Witkowski, Kofman, Reardon, Han, Moore, Elmarakeby, Salari, Choudhry, Al-Sulaiman, Taylor-Weiner, Van Allen.
Drafting of the manuscript: AlDubayan, Conway, Camp, Han, Taylor-Weiner, Van Allen.
Critical revision of the manuscript for important intellectual content: AlDubayan, Conway, Witkowski, Kofman, Reardon, Moore, Elmarakeby, Salari, Choudhry, Al-Rubaish, Al-Sulaiman, Al-Ali, Taylor-Weiner, Van Allen.
Statistical analysis: AlDubayan, Conway, Camp, Kofman, Reardon, Han, Elmarakeby, Salari, Choudhry, Taylor-Weiner, Van Allen.
Obtained funding: AlDubayan, Van Allen.
Administrative, technical, or material support: Moore, Al-Rubaish, Al-Sulaiman, Al-Ali, Van Allen.
Supervision: AlDubayan, Taylor-Weiner, Van Allen.
Conflict of Interest Disclosures: Dr Moore reported receiving personal fees from Immunity Health. Dr Van Allen reported serving on advisory boards or as a consultant to Tango Therapeutics, Genome Medical, Invitae, Illumina, Manifold Bio, Monte Rosa Therapeutics, and Enara Bio; receiving personal fees from Invitae, Tango Therapeutics, Genome Medical, Ervaxx, Roche/Genentech, and Janssen; receiving research support from Novartis and Bristol-Myers Squibb; having equity in Tango Therapeutics, Genome Medical, Syapse, Enara Bio, Manifold Bio, and Microsoft; receiving travel reimbursement from Roche and Genentech; and filing institutional patents (for ERCC2 variants and chemotherapy response, chromatin variants and immunotherapy response, and methods for clinical interpretation). No other disclosures were reported.
Funding/Support: This work was supported by Conquer Cancer Foundation Career Development Award 13167 from the American Society of Clinical Oncology (awarded to Dr AlDubayan), Young Investigator Award 18YOUN02 from the Prostate Cancer Foundation (awarded to Dr AlDubayan), the Challenge Award from the PCF-V Foundation (awarded to Dr Van Allen), the Emerging Leader Award from the Mark Foundation (awarded to Dr Van Allen), grant R01CA222574 from the National Institutes of Health (awarded to Dr Van Allen), and grant 12-MED2224-46 (for science and technology) from King Abdulaziz City (awarded to Drs Al-Rubaish, Al-Sulaiman, and Al-Ali).
Role of the Funder/Sponsor: The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank all the individuals who participated in this study. We also thank Eric Banks, PhD (data sciences platform, Broad Institute of Massachusetts Institute of Technology and Harvard University; no compensation was received), for his valuable insight into the underlying model of the Genome Analysis Toolkit and for his comments on the results of this study. We also thank Jeff Kohlwes, MD, MPH (general internal medicine, University of California, San Francisco; no compensation was received), Aaron Neinstein, MD (endocrinology and clinical informatics, University of California, San Francisco; no compensation was received), and Tara Vijayan, MD (infectious disease, University of California, Los Angeles; no compensation was received), for their feedback on the content in the manuscript.
Additional Information: The results are based, in part, on data generated by the Cancer Genome Atlas managed by the National Cancer Institute and the National Human Genome Research Institute. Information about the Cancer Genome Atlas can be found at http://cancergenome.nih.gov. The raw sequence data can be obtained through dbGaP (https://www.ncbi.nlm.nih.gov/gap) or as described in the original articles (details appear in the Methods section). All software tools used in this study are publicly available.
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