Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death
- Memorial Sloan Kettering Cancer Center, United States
- Memorial Sloan-Kettering Cancer Center, United States
- Icahn School of Medicine at Mount Sinai, United States
- Kings College London, United Kingdom
- Queen Mary University of London, United Kingdom
Abstract
The level of copy number alteration (CNA), termed CNA burden, in the tumor genome is associated with recurrence of primary prostate cancer. Whether CNA burden is associated with prostate cancer survival or outcomes in other cancers is unknown. We analyzed the CNA landscape of conservatively treated prostate cancer in a biopsy and transurethral resection cohort, reflecting an increasingly common treatment approach. We find that CNA burden is prognostic for cancer-specific death, independent of standard clinical prognostic factors. More broadly, we find CNA burden is significantly associated with disease-free and overall survival in primary breast, endometrial, renal clear cell, thyroid, and colorectal cancer in TCGA cohorts. To assess clinical applicability, we validated these findings in an independent pan-cancer cohort of patients whose tumors were sequenced using a clinically-certified next generation sequencing assay (MSK-IMPACT), where prognostic value varied based on cancer type. This prognostic association was affected by incorporating tumor purity in some cohorts. Overall, CNA burden of primary and metastatic tumors is a prognostic factor, potentially modulated by sample purity and measurable by current clinical sequencing.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files and reference materials. The conservative treatment TAPG copy number cohort array data was deposited in NCBI GEO under accession number GSE103665 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103665, reviewer access token czwruyesnzqbbyn).
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Copy number alteration burden is a pan-cancer prognostic factor associated with metastasis and death in conservatively treated prostate cancer: TAPG1 CNA cohort aCGH dataPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE103665).
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Charles L Sawyers
National Institutes of Health (CA193837)
- Charles L Sawyers
Prostate Cancer Foundation
- Kamlesh Yadav
National Institutes of Health (CA092629)
- Charles L Sawyers
National Institutes of Health (CA155169)
- Charles L Sawyers
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Michael R Green, Howard Hughes Medical Institute, University of Massachusetts Medical School, United States
Version history
- Received: April 5, 2018
- Accepted: August 13, 2018
- Accepted Manuscript published: September 4, 2018 (version 1)
- Version of Record published: September 19, 2018 (version 2)
- Version of Record updated: September 28, 2018 (version 3)
Copyright
© 2018, Hieronymus et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death
eLife 7:e37294.
https://doi.org/10.7554/eLife.37294
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