Copy number alteration burden predicts prostate cancer relapse Journal Article


Authors: Hieronymus, H.; Schultz, N.; Gopalan, A.; Carver, B. S.; Chang, M.; Xiao, Y.; Heguy, A.; Huberman, K.; Bernstein, M.; Assel, M.; Murali, R.; Vickers, A.; Scardino, P. T.; Sander, C.; Reuter, V.; Taylor, B. S.; Sawyers, C. L.
Article Title: Copy number alteration burden predicts prostate cancer relapse
Abstract: Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discover prognostic biomarkers. Previously, we found an association between relapse and the pattern of DNA copy number alteration (CNA) in 168 primary tumors, raising the possibility of CNA as a prognostic biomarker. Here we examine this question by profiling an additional 104 primary prostate cancers and updating the initial 168 patient cohort with long-term clinical outcome. We find that CNA burden across the genome, defined as the percentage of the tumor genome affected by CNA, was associated with biochemical recurrence and metastasis after surgery in these two cohorts, independent of the prostate-specific antigen biomarker or Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, CNA burden was associated with biochemical recurrence in intermediate-risk Gleason 7 prostate cancers, independent of prostate-specific antigen or nomogram score. We further demonstrate that CNA burden can be measured in diagnostic needle biopsies using low-input whole-genome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts.
Keywords: controlled study; human tissue; major clinical study; cancer recurrence; cancer risk; follow up; prostate specific antigen; metastasis; oncology; prostate cancer; gleason score; needle biopsy; genomics; gene dosage; copy number alteration; cancer prognosis; prognosis; human; male; priority journal; article
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 111
Issue: 30
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2014-07-29
Start Page: 11139
End Page: 11144
Language: English
DOI: 10.1073/pnas.1411446111
PROVIDER: scopus
PMCID: PMC4121784
PUBMED: 25024180
DOI/URL:
Notes: Export Date: 2 September 2014 -- CODEN: PNASA -- Source: Scopus
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MSK Authors
  1. Charles L Sawyers
    155 Sawyers
  2. Adriana Heguy
    85 Heguy
  3. Peter T Scardino
    621 Scardino
  4. Anuradha Gopalan
    274 Gopalan
  5. Andrew J Vickers
    560 Vickers
  6. Yonghong Xiao
    6 Xiao
  7. Rajmohan Murali
    156 Murali
  8. Brett Stewart Carver
    109 Carver
  9. Chris Sander
    196 Sander
  10. Victor Reuter
    913 Reuter
  11. Nikolaus D Schultz
    202 Schultz
  12. Melissa Jean Assel
    39 Assel
  13. Matthew   Chang
    21 Chang