Copy Number Loss of 17q22 Is Associated with Enzalutamide Resistance and Poor Prognosis in Metastatic Castration-Resistant Prostate Cancer.
Benzamides
/ pharmacology
Biomarkers, Tumor
/ genetics
Biopsy
Chromosomes, Human, Pair 17
/ genetics
DNA Copy Number Variations
Disease-Free Survival
Drug Resistance, Neoplasm
/ genetics
Humans
Male
Nitriles
/ pharmacology
Phenylthiohydantoin
/ pharmacology
Prostate
/ pathology
Prostatic Neoplasms, Castration-Resistant
/ drug therapy
RNA-Seq
Survival Analysis
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
16
07
2019
revised:
24
05
2020
accepted:
29
06
2020
pubmed:
31
7
2020
medline:
26
11
2021
entrez:
31
7
2020
Statut:
ppublish
Résumé
The purpose of this study was to measure genomic changes that emerge with enzalutamide treatment using analyses of whole-genome sequencing and RNA sequencing. One hundred and one tumors from men with metastatic castration-resistant prostate cancer (mCRPC) who had not been treated with enzalutamide ( Copy number loss was more common than gain in enzalutamide-resistant tumors. Specially, we identified 124 protein-coding genes that were more commonly lost in enzalutamide-resistant samples. These 124 genes included eight putative tumor suppressors located at nine distinct genomic regions. We demonstrated that focal deletion of the 17q22 locus that includes Copy number loss is common in enzalutamide-resistant tumors. Focal deletion of chromosome 17q22 defines a previously unappreciated molecular subset of enzalutamide-resistant mCRPC associated with poor clinical outcome.
Identifiants
pubmed: 32727885
pii: 1078-0432.CCR-19-2303
doi: 10.1158/1078-0432.CCR-19-2303
pmc: PMC7484240
mid: NIHMS1609735
doi:
Substances chimiques
Benzamides
0
Biomarkers, Tumor
0
Nitriles
0
Phenylthiohydantoin
2010-15-3
enzalutamide
93T0T9GKNU
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
4616-4624Subventions
Organisme : NLM NIH HHS
ID : K01 LM012877
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA093373
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097186
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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