Decoding the evolutionary response to prostate cancer therapy by plasma genome sequencing.
Liquid biopsies
Non-invasive
Tumor evolution
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
06 07 2020
06 07 2020
Historique:
received:
03
01
2020
accepted:
13
05
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
8
7
2021
Statut:
epublish
Résumé
Investigating genome evolution in response to therapy is difficult in human tissue samples. To address this challenge, we develop an unbiased whole-genome plasma DNA sequencing approach that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach is applied to study longitudinal blood plasma samples from prostate cancer patients, where longitudinal tissue biopsies from the bone and other metastatic sites have been challenging to collect. A molecular characterization of archival plasma DNA from 233 patients and genomic profiling of 101 patients identifies clinical correlations of aneuploid plasma DNA profiles with poor survival, increased plasma DNA concentrations, and lower plasma DNA size distributions. Deep-exome sequencing and genomic copy number profiling are performed on 23 patients, including 9 patients with matched metastatic tissues and 12 patients with serial plasma samples. These data show a high concordance in genomic alterations between the plasma DNA and metastatic tissue samples, suggesting the plasma DNA is highly representative of the tissue alterations. Longitudinal sequencing of 12 patients with 2-5 serial plasma samples reveals clonal dynamics and genome evolution in response to hormonal and chemotherapy. By performing an integrated evolutionary analysis, minor subclones are identified in 9 patients that expanded in response to therapy and harbored mutations associated with resistance. This study provides an unbiased evolutionary approach to non-invasively delineate clonal dynamics and identify clones with mutations associated with resistance in prostate cancer.
Sections du résumé
BACKGROUND
Investigating genome evolution in response to therapy is difficult in human tissue samples. To address this challenge, we develop an unbiased whole-genome plasma DNA sequencing approach that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach is applied to study longitudinal blood plasma samples from prostate cancer patients, where longitudinal tissue biopsies from the bone and other metastatic sites have been challenging to collect.
RESULTS
A molecular characterization of archival plasma DNA from 233 patients and genomic profiling of 101 patients identifies clinical correlations of aneuploid plasma DNA profiles with poor survival, increased plasma DNA concentrations, and lower plasma DNA size distributions. Deep-exome sequencing and genomic copy number profiling are performed on 23 patients, including 9 patients with matched metastatic tissues and 12 patients with serial plasma samples. These data show a high concordance in genomic alterations between the plasma DNA and metastatic tissue samples, suggesting the plasma DNA is highly representative of the tissue alterations. Longitudinal sequencing of 12 patients with 2-5 serial plasma samples reveals clonal dynamics and genome evolution in response to hormonal and chemotherapy. By performing an integrated evolutionary analysis, minor subclones are identified in 9 patients that expanded in response to therapy and harbored mutations associated with resistance.
CONCLUSIONS
This study provides an unbiased evolutionary approach to non-invasively delineate clonal dynamics and identify clones with mutations associated with resistance in prostate cancer.
Identifiants
pubmed: 32631448
doi: 10.1186/s13059-020-02045-9
pii: 10.1186/s13059-020-02045-9
pmc: PMC7336456
doi:
Substances chimiques
Antineoplastic Agents
0
Cell-Free Nucleic Acids
0
Types de publication
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
162Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : National Cancer Institute (US)
ID : RO1CA240526
Pays : International
Organisme : NCI NIH HHS
ID : P50 CA140388
Pays : United States
Références
Cell. 2015 May 21;161(5):1215-1228
pubmed: 26000489
Cell. 2014 Sep 25;159(1):176-187
pubmed: 25201530
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Cancer Discov. 2014 Jun;4(6):650-61
pubmed: 24801577
Sci Rep. 2018 Jan 30;8(1):1917
pubmed: 29382943
Front Oncol. 2018 Aug 06;8:297
pubmed: 30128304
Bioinformatics. 2011 Oct 1;27(19):2648-54
pubmed: 21828086
Cell. 2015 Jul 16;162(2):454
pubmed: 28843286
Bioinformatics. 2007 Mar 15;23(6):657-63
pubmed: 17234643
Nature. 2017 Jan 19;541(7637):359-364
pubmed: 28068672
Nat Rev Cancer. 2004 Mar;4(3):177-83
pubmed: 14993899
Biomed Res Int. 2017;2017:2593674
pubmed: 28280729
Sci Rep. 2018 May 9;8(1):7375
pubmed: 29743667
Nat Med. 2016 Apr;22(4):369-78
pubmed: 26928463
Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
pubmed: 12824425
Cell. 2017 Feb 9;168(4):613-628
pubmed: 28187284
Eur Urol. 2019 Mar;75(3):378-382
pubmed: 30337059
Cancer Cell. 2010 Jul 13;18(1):11-22
pubmed: 20579941
Nat Commun. 2017 Nov 6;8(1):1324
pubmed: 29109393
Rev Urol. 2008 Fall;10(4):262-80
pubmed: 19145270
PLoS One. 2015 Oct 16;10(10):e0140712
pubmed: 26474073
Sci Transl Med. 2018 Nov 7;10(466):
pubmed: 30404863
J Natl Cancer Inst. 2017 Dec 1;109(12):
pubmed: 29206995
Cancer Cell. 2018 Dec 10;34(6):996-1011.e8
pubmed: 30537516
PLoS One. 2014 Aug 01;9(8):e101777
pubmed: 25084170
Nat Methods. 2014 Apr;11(4):396-8
pubmed: 24633410
Clin Chem. 2017 Feb;63(2):532-541
pubmed: 27940449
Nat Med. 2019 Sep;25(9):1415-1421
pubmed: 31501609
Cancer Med. 2018 May;7(5):1988-2002
pubmed: 29608247
PLoS One. 2011;6(8):e23144
pubmed: 21829708
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436
pubmed: 31061129
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17087-92
pubmed: 21949389
Nucleic Acids Res. 2011 Jan;39(Database issue):D945-50
pubmed: 20952405
Methods Mol Biol. 2019;1908:243-264
pubmed: 30649733
Nat Commun. 2016 Jun 22;7:12008
pubmed: 27328849
Sci Transl Med. 2014 Feb 19;6(224):224ra24
pubmed: 24553385
J Transl Med. 2016 Apr 19;14:95
pubmed: 27095081
Nature. 2012 Jul 12;487(7406):239-43
pubmed: 22722839
Eur Urol. 2018 Mar;73(3):322-339
pubmed: 28927585
Br J Cancer. 2017 Jul 25;117(3):409-420
pubmed: 28641312
Bioinformatics. 2015 May 1;31(9):1349-56
pubmed: 25568283
Cell. 2013 Apr 25;153(3):666-77
pubmed: 23622249
Mol Oncol. 2016 Mar;10(3):464-74
pubmed: 26776681
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
JCO Precis Oncol. 2018;2018:
pubmed: 29376144
Bioinformatics. 2014 Dec 15;30(24):3532-40
pubmed: 25297070
Nat Med. 2016 Mar;22(3):298-305
pubmed: 26855148
Mol Cell Probes. 2019 Aug;46:101411
pubmed: 31173881
Biochim Biophys Acta Rev Cancer. 2017 Apr;1867(2):151-161
pubmed: 28110020
Curr Opin Urol. 2016 Sep;26(5):472-80
pubmed: 27214580
Cancer Res. 2006 Mar 15;66(6):3114-9
pubmed: 16540661
Nature. 2011 Apr 7;472(7341):90-4
pubmed: 21399628
Nat Genet. 2018 May;50(5):645-651
pubmed: 29610475
J Clin Oncol. 2018 Feb 20;36(6):543-553
pubmed: 29298117
Curr Treat Options Oncol. 2018 Nov 15;19(12):1
pubmed: 30535808
Anticancer Res. 2017 Jan;37(1):125-134
pubmed: 28011482
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34
pubmed: 25199790
Nature. 2017 Apr 26;545(7655):446-451
pubmed: 28445469
Cell. 2015 Nov 5;163(4):1011-25
pubmed: 26544944
Oncotarget. 2017 Sep 19;8(50):88211-88231
pubmed: 29152153
Nat Biotechnol. 2014 May;32(5):479-84
pubmed: 24752078
JCO Precis Oncol. 2017 Jul;2017:
pubmed: 28825054
Expert Opin Emerg Drugs. 2018 Jun;23(2):123-133
pubmed: 29595348
Nat Rev Cancer. 2017 Apr;17(4):223-238
pubmed: 28233803
Eur Urol Focus. 2019 Mar;5(2):147-154
pubmed: 30772358
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3178-9
pubmed: 25733911
Nat Rev Drug Discov. 2015 Aug;14(8):543-60
pubmed: 26111766
Proc Natl Acad Sci U S A. 2014 Jul 29;111(30):11139-44
pubmed: 25024180
Nat Rev Cancer. 2012 Apr 19;12(5):323-34
pubmed: 22513401
Curr Protoc Hum Genet. 2013 Jan;Chapter 7:Unit7.20
pubmed: 23315928
Prostate. 2019 Jun;79(8):920-928
pubmed: 30908670
Nat Genet. 2012 May 20;44(6):685-9
pubmed: 22610119
Oncotarget. 2015 Jun 30;6(18):16411-21
pubmed: 25915538