Germline Mutations in DNA Repair Genes in Patients With Metastatic Castration-resistant Prostate Cancer.
DNA repair genes
Prostate cancer
germline mutations
next generation sequencing
Journal
In vivo (Athens, Greece)
ISSN: 1791-7549
Titre abrégé: In Vivo
Pays: Greece
ID NLM: 8806809
Informations de publication
Date de publication:
Historique:
received:
19
03
2020
revised:
30
03
2020
accepted:
31
03
2020
entrez:
2
7
2020
pubmed:
2
7
2020
medline:
22
6
2021
Statut:
ppublish
Résumé
The aim of this study was to analyse the genetic profiles of metastatic castration-resistant prostate cancer (mCRPC) by using next generation sequencing to identify variants with pathogenic potential in nine DNA repair genes - BRCA1, BRCA2, RAD50, RAD51, RAD51C/D, ATM and ATR. Isolated genomic DNA from peripheral blood of 50 patients with mCRPC was used for the sequencing of 111 genes associated with hereditary cancer on an Illumina platform. Identified variants were tested in Integrative Genomic Viewer, their clinical significance confirmed in databases and their potential impact on protein function predicted by in silico tools. From nine analysed DNA repair genes, we identified 14 relevant variants; three pathogenic variants - BRCA2 (rs80359306), RAD50 (rs786201531) and ATM (rs1555099760), and eleven other variants with pathogenic potential. The pathogenic variants identified in this study are located in evolutionarily conserved regions of proteins and are highly likely to affect DNA repair efficiency.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
The aim of this study was to analyse the genetic profiles of metastatic castration-resistant prostate cancer (mCRPC) by using next generation sequencing to identify variants with pathogenic potential in nine DNA repair genes - BRCA1, BRCA2, RAD50, RAD51, RAD51C/D, ATM and ATR.
MATERIALS AND METHODS
METHODS
Isolated genomic DNA from peripheral blood of 50 patients with mCRPC was used for the sequencing of 111 genes associated with hereditary cancer on an Illumina platform. Identified variants were tested in Integrative Genomic Viewer, their clinical significance confirmed in databases and their potential impact on protein function predicted by in silico tools.
RESULTS
RESULTS
From nine analysed DNA repair genes, we identified 14 relevant variants; three pathogenic variants - BRCA2 (rs80359306), RAD50 (rs786201531) and ATM (rs1555099760), and eleven other variants with pathogenic potential.
CONCLUSION
CONCLUSIONS
The pathogenic variants identified in this study are located in evolutionarily conserved regions of proteins and are highly likely to affect DNA repair efficiency.
Identifiants
pubmed: 32606146
pii: 34/4/1773
doi: 10.21873/invivo.11971
pmc: PMC7439863
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1773-1778Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Références
Nat Protoc. 2016 Jan;11(1):1-9
pubmed: 26633127
Anticancer Res. 2019 Oct;39(10):5353-5359
pubmed: 31570429
Fam Cancer. 2010 Sep;9(3):267-74
pubmed: 20383589
Gastroenterology. 2015 Sep;149(3):604-13.e20
pubmed: 25980754
PLoS Genet. 2016 Aug 04;12(8):e1006236
pubmed: 27490902
Breast Cancer Res Treat. 2017 Feb;161(3):575-586
pubmed: 28008555
J Oncol. 2019 May 2;2019:2976373
pubmed: 31186630
Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515
pubmed: 30395287
Mutagenesis. 2005 Nov;20(6):433-40
pubmed: 16236763
Oncol Rep. 2008 Jan;19(1):263-8
pubmed: 18097605
Cold Spring Harb Perspect Biol. 2015 Apr 01;7(4):a016600
pubmed: 25833843
Hered Cancer Clin Pract. 2016 Feb 03;14:5
pubmed: 26843898
Breast Cancer Res Treat. 2011 Oct;129(3):939-46
pubmed: 21537932
Environ Mol Mutagen. 2001;37(3):241-83
pubmed: 11317342
Breast Cancer Res Treat. 2014 Aug;147(1):133-43
pubmed: 25086635
J Clin Oncol. 2016 May 1;34(13):1460-8
pubmed: 26976419
Nat Commun. 2016 Sep 15;7:12813
pubmed: 27628236
Cell Cycle. 2016;15(8):1117-24
pubmed: 27097373
Prostate Cancer Prostatic Dis. 2019 Sep;22(3):406-410
pubmed: 30542053
Curr Biol. 2009 Mar 24;19(6):524-9
pubmed: 19268590
J Clin Oncol. 2016 Dec;34(34):4071-4078
pubmed: 27621404
Cancers (Basel). 2019 Mar 12;11(3):
pubmed: 30871108
Genet Med. 2017 Oct;19(10):1105-1117
pubmed: 28492532
Hum Mol Genet. 2012 Jul 1;21(13):2889-98
pubmed: 22451500
EMBO J. 2003 Oct 15;22(20):5612-21
pubmed: 14532133
Cell Cycle. 2011 Aug 1;10(15):2461-70
pubmed: 21734457
BMC Cancer. 2013 May 17;13:243
pubmed: 23683081
Curr Probl Cancer. 2017 Jul - Aug;41(4):287-301
pubmed: 28712484
Nat Methods. 2014 Apr;11(4):361-2
pubmed: 24681721
Cancer. 2018 Aug 1;124(15):3105-3117
pubmed: 29669169
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
J Biol Chem. 2005 Feb 11;280(6):4029-36
pubmed: 15546863
Asian J Androl. 2012 May;14(3):409-14
pubmed: 22522501
BMC Cancer. 2018 Feb 13;18(1):179
pubmed: 29433453
Int J Clin Exp Pathol. 2014 Aug 15;7(9):6262-9
pubmed: 25337278
Curr Oncol Rep. 2019 Mar 27;21(5):42
pubmed: 30919167
Bioinformatics. 2019 Jun 1;35(11):1978-1980
pubmed: 30376034
Br J Cancer. 2011 Oct 11;105(8):1230-4
pubmed: 21952622