Aneuploidy drives lethal progression in prostate cancer

Abstract

Aneuploidy is usually quantified by measuring intracellular DNA content or chromosome structure and number. We show that the number of altered chromosome arms can be estimated from transcriptome profiling, which allows for assessing aneuploidy within repositories of archival, formalin-fixed, paraffin-embedded tumors. While aneuploidy impedes proliferation in primary cells, we show that it is a feature of aggressiveness in primary prostate cancers that are more likely to become lethal. Our data suggest that losses or gains of entire chromosome arms confers aggressiveness beyond affecting copy numbers of tumor suppressors or oncogenes on those arms. Beyond helping understand the etiology of aggressive prostate cancer, we propose that extent of aneuploidy could also be employed clinically to inform risk stratification and treatment.

Document Details

Document Type
Pub Defense Publication
Publication Date
May 13, 2019
Source ID
10.1073/pnas.1902645116

Entities

People

  • Angelika Amon
  • Charles A Whittaker
  • Konrad H Stopsack
  • Lorelei A. Mucci
  • Massimo Loda
  • Philip W. Kantoff
  • Travis A. Gerke

Organizations

  • Dana–Farber Cancer Institute
  • H. Lee Moffitt Cancer Center & Research Institute
  • Harvard Medical School
  • Harvard University
  • Howard Hughes Medical Institute
  • Massachusetts Institute of Technology
  • Memorial Sloan Kettering Cancer Center
  • National Cancer Institute
  • National Institute of General Medical Sciences
  • Prostate Cancer Foundation
  • United States Department of Defense

Tags

Readers

  • Molecular Biology and Genetics
  • Oncology and Biomarker-Based Cancer Detection.