Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential
Abstract
Metastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning > 300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 07, 2020
- Source ID
- 10.1186/s12885-020-06817-1
Entities
People
- Beatrice S Knudsen
- Catherine S. Grasso
- Eric T. Miller
- Isla P Garraway
- Jennelle Hodge
- Junhee Yoon
- Lorna Kwan
- Michael J. Quist
- Michael Lewis
- Michael R Freeman
- Minhyung Kim
- Radu M. Cadaneanu
- Sandy T. Liu
- Sungyong You
- Xinmin Li
Organizations
- Jean Perkins Foundation
- Movember Foundation
- National Cancer Institute
- Prostate Cancer Foundation
- United States Department of Defense