Single-Cell Circulating Tumor Cell Analysis Reveals Genomic Instability as a Distinctive Feature of Aggressive Prostate Cancer.
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Biomarkers, Tumor
/ genetics
Carboplatin
/ administration & dosage
DNA Copy Number Variations
Genes, Tumor Suppressor
Genomic Instability
Humans
Male
Middle Aged
Neoplastic Cells, Circulating
/ pathology
Progression-Free Survival
Prostate
Prostatic Neoplasms
/ blood
Single-Cell Analysis
Taxoids
/ administration & dosage
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 08 2020
01 08 2020
Historique:
received:
16
12
2019
revised:
25
02
2020
accepted:
22
04
2020
pubmed:
29
4
2020
medline:
3
11
2021
entrez:
29
4
2020
Statut:
ppublish
Résumé
Aggressive variant prostate cancer (AVPC) represents a clinical subset distinguished by therapy resistance and poor prognosis, linked to combined losses of the tumor suppressor genes (TSG) Genomic analysis of chromosomal copy-number alterations (CNA) at single-cell resolution was performed in CTC from patients with and without AVPC before initiating chemotherapy with cabazitaxel or cabazitaxel and carboplatin. We evaluated associations between single-CTC genomics and clinical features, progression-free survival, and overall survival. A total of 257 individual CTC were sequenced from 47 patients (1-22 CTC/patient). Twenty patients (42.6%) had concurrent 2+TSG losses in at least one CTC in association with poor survival and increased genomic instability, inferred by high large-scale transitions scores. Higher LST in CTC were independent of CTC enumerated, clinically more indicative of aggressive behavior than co-occurring TSG losses, and molecularly associated with gains in chromosomal regions including Our findings suggest that genomic instability in CTC is a hallmark of advanced prostate cancer aggressiveness, and support single-CTC sequencing as a compelling tool to noninvasively characterize cancer heterogeneity.
Identifiants
pubmed: 32341031
pii: 1078-0432.CCR-19-4100
doi: 10.1158/1078-0432.CCR-19-4100
pmc: PMC8043601
mid: NIHMS1621435
doi:
Substances chimiques
Biomarkers, Tumor
0
Taxoids
0
cabazitaxel
51F690397J
Carboplatin
BG3F62OND5
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4143-4153Subventions
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
Références
Nat Commun. 2017 Nov 13;8(1):1470
pubmed: 29133916
N Engl J Med. 2014 Jul 31;371(5):424-33
pubmed: 24881730
Clin Cancer Res. 2019 Mar 15;25(6):1766-1773
pubmed: 30209161
Cell. 2018 May 3;173(4):1003-1013.e15
pubmed: 29681457
Cancer Res. 2006 Aug 15;66(16):7889-98
pubmed: 16912162
Nat Genet. 2018 May;50(5):645-651
pubmed: 29610475
Urol Oncol. 2017 Aug;35(8):535
pubmed: 28623072
N Engl J Med. 2013 Jan 10;368(2):138-48
pubmed: 23228172
Clin Cancer Res. 2013 Jul 1;19(13):3621-30
pubmed: 23649003
Eur Urol. 2019 Jul;76(1):89-97
pubmed: 30553611
Cell. 2018 Jul 26;174(3):758-769.e9
pubmed: 30033370
Control Clin Trials. 1993 Dec;14(6):511-22
pubmed: 8119066
PLoS One. 2016 Nov 16;11(11):e0165089
pubmed: 27851748
N Engl J Med. 2018 Feb 15;378(7):645-657
pubmed: 29412780
J Clin Invest. 2014 Nov;124(11):5013-26
pubmed: 25295534
Science. 2017 Jan 6;355(6320):78-83
pubmed: 28059767
J Clin Oncol. 2018 Aug 20;36(24):2492-2503
pubmed: 29985747
Cancer Cell. 2010 Jul 13;18(1):11-22
pubmed: 20579941
Cancer Discov. 2018 Apr;8(4):444-457
pubmed: 29367197
Lancet Oncol. 2019 Oct;20(10):1432-1443
pubmed: 31515154
Clin Cancer Res. 2016 Mar 15;22(6):1510-9
pubmed: 26671992
J Clin Invest. 2019 Jul 30;129(10):4492-4505
pubmed: 31361600
Clin Cancer Res. 2014 Feb 15;20(4):890-903
pubmed: 24323898
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436
pubmed: 31061129
Cancer Res. 2013 Jul 15;73(14):4247-55
pubmed: 23687339
Science. 2017 Jan 6;355(6320):84-88
pubmed: 28059768
J Natl Cancer Inst. 2015 Nov 27;108(2):
pubmed: 26615022
Nat Biotechnol. 2018 Dec 03;:
pubmed: 30531897
Nat Med. 2016 Mar;22(3):298-305
pubmed: 26855148
Eur Urol. 2019 Nov;76(5):562-571
pubmed: 30928160
Clin Cancer Res. 2017 Apr 1;23(7):1722-1732
pubmed: 27702818
Nat Rev Clin Oncol. 2019 Feb;16(2):81-104
pubmed: 30356138
Cancer Res. 2017 Oct 15;77(20):5687-5698
pubmed: 28819021
Cell. 2018 Jul 12;174(2):433-447.e19
pubmed: 29909985
Eur Urol. 2017 Jun;71(6):874-882
pubmed: 27979426
Phys Biol. 2012 Feb;9(1):016003
pubmed: 22306768
Clin Cancer Res. 2016 Mar 15;22(6):1520-30
pubmed: 26546618