The Impact of Whole Genome Data on Therapeutic Decision-Making in Metastatic Prostate Cancer: A Retrospective Analysis.
optical mapping
precision medicine
prostate cancer
therapy
whole genome sequencing
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
07 May 2020
07 May 2020
Historique:
received:
18
03
2020
revised:
21
04
2020
accepted:
28
04
2020
entrez:
13
5
2020
pubmed:
13
5
2020
medline:
13
5
2020
Statut:
epublish
Résumé
While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to individualize treatment. Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients; whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants. Tumour samples were derived from prostate, lymph nodes, bone and brain. Most samples had acquired genomic alterations in multiple therapeutically relevant pathways, including DNA damage response (11/13 cases), PI3K (7/13), MAPK (10/13) and Wnt (9/13). Five patients had somatic copy number losses in genes that may indicate sensitivity to immunotherapy ( Most cases, whether primary or metastatic, harboured therapeutically relevant alterations, including those associated with PARP inhibitor sensitivity, immunotherapy sensitivity and resistance to androgen pathway targeting agents. The observed intra-patient heterogeneity and presence of genomic alterations in multiple growth pathways in individual cases suggests that a precision medicine model in prostate cancer needs to simultaneously incorporate multiple pathway-targeting agents. Our whole genome approach allowed for structural variant assessment in addition to the ability to rapidly reassess an individual's molecular landscape as knowledge of relevant biomarkers evolve. This retrospective oncological assessment highlights the genomic complexity of prostate cancer and the potential impact of assessing genomic data for an individual at any stage of the disease.
Sections du résumé
BACKGROUND
BACKGROUND
While critical insights have been gained from evaluating the genomic landscape of metastatic prostate cancer, utilizing this information to inform personalized treatment is in its infancy. We performed a retrospective pilot study to assess the current impact of precision medicine for locally advanced and metastatic prostate adenocarcinoma and evaluate how genomic data could be harnessed to individualize treatment.
METHODS
METHODS
Deep whole genome-sequencing was performed on 16 tumour-blood pairs from 13 prostate cancer patients; whole genome optical mapping was performed in a subset of 9 patients to further identify large structural variants. Tumour samples were derived from prostate, lymph nodes, bone and brain.
RESULTS
RESULTS
Most samples had acquired genomic alterations in multiple therapeutically relevant pathways, including DNA damage response (11/13 cases), PI3K (7/13), MAPK (10/13) and Wnt (9/13). Five patients had somatic copy number losses in genes that may indicate sensitivity to immunotherapy (
CONCLUSIONS
CONCLUSIONS
Most cases, whether primary or metastatic, harboured therapeutically relevant alterations, including those associated with PARP inhibitor sensitivity, immunotherapy sensitivity and resistance to androgen pathway targeting agents. The observed intra-patient heterogeneity and presence of genomic alterations in multiple growth pathways in individual cases suggests that a precision medicine model in prostate cancer needs to simultaneously incorporate multiple pathway-targeting agents. Our whole genome approach allowed for structural variant assessment in addition to the ability to rapidly reassess an individual's molecular landscape as knowledge of relevant biomarkers evolve. This retrospective oncological assessment highlights the genomic complexity of prostate cancer and the potential impact of assessing genomic data for an individual at any stage of the disease.
Identifiants
pubmed: 32392735
pii: cancers12051178
doi: 10.3390/cancers12051178
pmc: PMC7280976
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Cell. 2018 Jul 26;174(3):758-769.e9
pubmed: 30033370
Nat Biotechnol. 2016 Feb;34(2):155-63
pubmed: 26619011
Genome Biol. 2015 Feb 13;16:35
pubmed: 25786235
J Clin Oncol. 2018 Oct 20;36(30):3007-3014
pubmed: 29733771
Nat Commun. 2018 Aug 17;9(1):3292
pubmed: 30120226
Cell. 2015 May 21;161(5):1215-1228
pubmed: 26000489
Clin Cancer Res. 2019 Feb 1;25(3):928-936
pubmed: 30037818
Oncol Lett. 2016 Dec;12(6):4305-4311
pubmed: 28105146
Eur Urol Oncol. 2018 Dec;1(6):449-458
pubmed: 31158087
Br J Cancer. 2010 Sep 7;103(6):918-24
pubmed: 20736950
Ann Oncol. 2015 Jan;26(1):64-70
pubmed: 25319062
PLoS One. 2013 Oct 30;8(10):e77945
pubmed: 24205039
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Cancer Treat Rev. 2017 Mar;54:68-73
pubmed: 28231559
Eur Urol. 2017 May;71(5):740-747
pubmed: 27989354
J Clin Oncol. 2013 May 10;31(14):1748-57
pubmed: 23569316
J Urol. 2011 Mar;185(3):869-75
pubmed: 21239008
Bioinformatics. 2018 Oct 1;34(19):3380-3381
pubmed: 29771315
PLoS One. 2013;8(2):e55864
pubmed: 23405223
J Neuroimaging. 2014 Mar-Apr;24(2):161-6
pubmed: 23279641
Eur Urol. 2017 Jul;72(1):34-42
pubmed: 28259476
Nat Biotechnol. 2012 Aug;30(8):771-6
pubmed: 22797562
Nat Genet. 2015 Jul;47(7):736-45
pubmed: 26005866
Zhonghua Nan Ke Xue. 2012 Jun;18(6):499-503
pubmed: 22774602
JAMA Oncol. 2017 Apr 01;3(4):524-548
pubmed: 27918777
Cancer. 2017 Jul 1;123(13):2489-2496
pubmed: 28323339
Clin Cancer Res. 2012 Aug 1;18(15):4173-82
pubmed: 22693357
Ann Oncol. 2017 Oct 01;28(10):2472-2480
pubmed: 28961847
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Cell. 2018 Jun 14;173(7):1770-1782.e14
pubmed: 29906450
Genome Res. 2014 Nov;24(11):1881-93
pubmed: 25060187
Nat Med. 2019 May;25(5):744-750
pubmed: 31011206
Cancer Sci. 2017 Oct;108(10):2011-2021
pubmed: 28771887
Clin Cancer Res. 2016 Aug 1;22(15):3937-49
pubmed: 26968201
Nat Commun. 2019 Mar 4;10(1):1025
pubmed: 30833565
Bioinformatics. 2016 Jan 15;32(2):292-4
pubmed: 26428292
Genome Biol. 2018 Sep 10;19(1):129
pubmed: 30201020
N Engl J Med. 2012 Mar 8;366(10):883-892
pubmed: 22397650
JAMA Oncol. 2019 May 01;5(5):623-632
pubmed: 30703190
Bioinformatics. 2015 Nov 15;31(22):3673-5
pubmed: 26163694
Proc Natl Acad Sci U S A. 2010 May 25;107(21):9742-6
pubmed: 20453196
Nat Rev Genet. 2007 Oct;8(10):735-48
pubmed: 17768402
Nature. 2016 May 02;534(7605):47-54
pubmed: 27135926
J Pathol. 2017 May;242(1):10-15
pubmed: 28127763
Genome Biol. 2014 Jun 26;15(6):R84
pubmed: 24970577
Nat Genet. 2007 May;39(5):645-9
pubmed: 17401363
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
J Urol. 2013 Jan;189(1):329-35
pubmed: 23174249
Prostate Cancer Prostatic Dis. 2018 Jun;21(2):260-268
pubmed: 29302046
PLoS Comput Biol. 2016 Apr 21;12(4):e1004873
pubmed: 27100738
Clin Cancer Res. 2019 Mar 15;25(6):1766-1773
pubmed: 30209161
Nat Commun. 2017 Oct 20;8(1):1081
pubmed: 29057879
Cancer Med. 2019 Aug;8(10):4644-4655
pubmed: 31270961
Nat Genet. 2008 Mar;40(3):281-3
pubmed: 18264098
Prostate Cancer Prostatic Dis. 2019 Dec;22(4):531-538
pubmed: 30804427
Genome Res. 2009 Sep;19(9):1639-45
pubmed: 19541911
N Engl J Med. 2017 Jul 27;377(4):338-351
pubmed: 28578639
Biomed Res Int. 2014;2014:380398
pubmed: 25045667
Cancer Cell. 2011 May 17;19(5):575-86
pubmed: 21575859
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Cancer Cell. 2009 Sep 8;16(3):246-58
pubmed: 19732724
Cancer Res. 2002 Feb 1;62(3):840-7
pubmed: 11830541
Eur Urol. 2018 Jun;73(6):890-896
pubmed: 29042125
Genome Res. 2017 Dec;27(12):2050-2060
pubmed: 29097403
Mol Cell Endocrinol. 2013 Jun 15;372(1-2):12-22
pubmed: 23523566
Nat Genet. 2018 May;50(5):682-692
pubmed: 29662167
Int J Oncol. 2019 Sep;55(3):597-616
pubmed: 31322208
Curr Mol Med. 2017;17(1):70-78
pubmed: 28231752
Oncotarget. 2019 Apr 12;10(28):2675-2692
pubmed: 31105869
Oncogene. 2017 Jul 13;36(28):4072-4080
pubmed: 28319070
J Biol Chem. 2005 Feb 25;280(8):6511-9
pubmed: 15598662
Drug Des Devel Ther. 2016 Jul 18;10:2311-21
pubmed: 27486308
Cancers (Basel). 2017 Apr 15;9(4):
pubmed: 28420128
Lancet. 2018 Dec 1;392(10162):2353-2366
pubmed: 30355464
Mol Cell Biol. 1998 Mar;18(3):1379-87
pubmed: 9488453
Cancer Cell. 2011 Jun 14;19(6):792-804
pubmed: 21620777
Eur Urol. 2019 Mar;75(3):498-505
pubmed: 30181068
Nat Genet. 2018 May;50(5):645-651
pubmed: 29610475
J Clin Oncol. 2019 May 10;37(14):1159-1168
pubmed: 30860948
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
J Biol Chem. 2006 May 19;281(20):14066-75
pubmed: 16565090
Am J Clin Exp Urol. 2014 Oct 02;2(3):169-87
pubmed: 25374920
Oncotarget. 2016 Nov 29;7(48):78804-78812
pubmed: 27788496
N Engl J Med. 2015 Aug 20;373(8):737-46
pubmed: 26244877
Lancet Oncol. 2020 Jan;21(1):162-174
pubmed: 31806540
J Pathol. 2004 Oct;204(2):159-66
pubmed: 15378487
Ann Oncol. 2017 Jul 01;28(7):1495-1507
pubmed: 28383660
Cell Mol Life Sci. 2011 Mar;68(6):1091-103
pubmed: 20812024
Cell. 2015 Nov 5;163(4):1011-25
pubmed: 26544944
Lancet. 2016 Mar 19;387(10024):1163-77
pubmed: 26719232
Cancer. 2017 Sep 15;123(18):3532-3539
pubmed: 28608931
Oncogene. 2008 Jul 17;27(31):4353-62
pubmed: 18372916
Nat Rev Clin Oncol. 2011 May;8(5):302-6
pubmed: 21468130
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Lancet Oncol. 2014 Dec;15(13):1521-1532
pubmed: 25456371
J Clin Oncol. 2020 Sep 10;38(26):3042-3050
pubmed: 32706639
Mol Cancer Res. 2019 Aug;17(8):1627-1638
pubmed: 31110158
Lab Invest. 2010 Jul;90(7):1060-7
pubmed: 20212450
N Engl J Med. 2015 Oct 29;373(18):1697-708
pubmed: 26510020
Eur Urol. 2020 Jan;77(1):14-21
pubmed: 31176623
Nat Methods. 2013 Nov;10(11):1081-2
pubmed: 24037244
Cell Res. 2018 Jul;28(7):719-729
pubmed: 29795445
Eur Urol. 2019 Oct;76(4):452-458
pubmed: 30797618
Cancer Discov. 2014 Aug;4(8):896-904
pubmed: 24866151
Br J Cancer. 2008 Jul 22;99(2):314-20
pubmed: 18594527
Eur Urol. 2015 Aug;68(2):186-93
pubmed: 25454609
Cell. 2018 Jul 12;174(2):422-432.e13
pubmed: 29909987
Prostate. 2019 Jun;79(8):920-928
pubmed: 30908670
Nat Commun. 2020 Jan 23;11(1):441
pubmed: 31974375
Brief Bioinform. 2013 Mar;14(2):178-92
pubmed: 22517427
Genome Res. 2012 Aug;22(8):1437-46
pubmed: 22665440
Clin Cancer Res. 2018 Nov 15;24(22):5585-5593
pubmed: 30068710
Cell. 2018 Jul 12;174(2):433-447.e19
pubmed: 29909985
Ann Oncol. 2013 May;24(5):1416-8
pubmed: 23524863
Lancet Oncol. 2013 Aug;14(9):882-92
pubmed: 23810788
Nat Genet. 2012 May 20;44(6):685-9
pubmed: 22610119
Cell Rep. 2018 Jan 16;22(3):796-808
pubmed: 29346775
Nat Commun. 2020 Feb 11;11(1):832
pubmed: 32047165