Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing.

Cell
Authors
Keywords
Abstract

Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with

Year of Publication
2018
Journal
Cell
Volume
174
Issue
2
Pages
433-447.e19
Date Published
2018 07 12
ISSN
1097-4172
DOI
10.1016/j.cell.2018.05.036
PubMed ID
29909985
PubMed Central ID
PMC6046279
Links
Grant list
R01 CA188228 / CA / NCI NIH HHS / United States
P50 CA090381 / CA / NCI NIH HHS / United States
MFE-140389 / CIHR / Canada
R01 CA174777 / CA / NCI NIH HHS / United States
P50 CA097186 / CA / NCI NIH HHS / United States
K08 CA188615 / CA / NCI NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
R01 CA215489 / CA / NCI NIH HHS / United States
R35 CA197568 / CA / NCI NIH HHS / United States
P01 CA163227 / CA / NCI NIH HHS / United States