Aneuploidy drives lethal progression in prostate cancer
Name
11390.full.pdf
Description
Published version
Size
1.28 MB
Format
Adobe PDF
Checksum (MD5)
56d037840ca34f861a585dd0d5ab0a7b
Author(s)
Stopsack, Konrad H.
Whittaker, Charles A.
Gerke, Travis A.
Loda, Massimo
Kantoff, Philip W.
Mucci, Lorelei A.
Amon, Angelika B
Date Issued
May 2019
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Stopsack, Konrad H. et al. "Aneuploidy drives lethal progression in prostate cancer." Proceedings of the National Academy of Sciences 116, 23 (May 2019): 11390-11395 © 2019 National Academy of Sciences
Version
Final published version
Abstract
Aneuploidy, defined as chromosome gains and losses, is a hallmark of cancer. However, compared with other tumor types, extensive aneuploidy is relatively rare in prostate cancer. Thus, whether numerical chromosome aberrations dictate disease progression in prostate cancer patients is not known. Here, we report the development of a method based on whole-transcriptome profiling that allowed us to identify chromosome-arm gains and losses in 333 primary prostate tumors. In two independent cohorts (n = 404) followed prospectively for metastases and prostate cancer-specific death for a median of 15 years, increasing extent of tumor aneuploidy as predicted from the tumor transcriptome was strongly associated with higher risk of lethal disease. The 23% of patients whose tumors had five or more predicted chromosome-arm alterations had 5.3 times higher odds of lethal cancer (95% confidence interval, 2.2 to 13.1) than those with the same Gleason score and no predicted aneuploidy. Aneuploidy was associated with lethality even among men with high-risk Gleason score 8-to-10 tumors. These results point to a key role of aneuploidy in driving aggressive disease in primary prostate cancer.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1902645116
