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.
authors.affiliation: Programs in Human Oncology and Pathogenesis and.
authors.forename: Haley
authors.initials: H
authors.lastname: Hieronymus
authors.affiliation: Computational Biology,Center for Molecular Oncology, and.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schultz
authors.affiliation: Departments of Pathology.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Gopalan
authors.affiliation: Urology, and.
authors.forename: Brett S
authors.initials: BS
authors.lastname: Carver
authors.affiliation: Department of Bioengineering and Therapeutic Sciences.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Chang
authors.affiliation: Departments of Pathology.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Programs in Human Oncology and Pathogenesis andDepartment of Pathology and Office for Collaborative Science, New York University Langone Medical Center, New York, NY 10016.
authors.forename: Adriana
authors.initials: A
authors.lastname: Heguy
authors.affiliation: Programs in Human Oncology and Pathogenesis andCenter for Molecular Oncology, and.
authors.forename: Kety
authors.initials: K
authors.lastname: Huberman
authors.affiliation: Urology, and.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bernstein
authors.affiliation: Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
authors.forename: Melissa
authors.initials: M
authors.lastname: Assel
authors.affiliation: Center for Molecular Oncology, andDepartments of Pathology.
authors.forename: Rajmohan
authors.initials: R
authors.lastname: Murali
authors.affiliation: Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
authors.forename: Andrew
authors.initials: A
authors.lastname: Vickers
authors.affiliation: Urology, and.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.affiliation: Computational Biology.
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.affiliation: Departments of Pathology.
authors.forename: Victor
authors.initials: V
authors.lastname: Reuter
authors.affiliation: Epidemiology and Biostatistics, andMedicine andHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143; and.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Taylor
authors.affiliation: Programs in Human Oncology and Pathogenesis and sawyersc@mskcc.org.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001707:Biopsy, Needle; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: genomics; oncology; prognosis