Detection of ctDNA with Personalized Molecular Barcode NGS and Its Clinical Significance in Patients with Early Breast Cancer.
Journal
Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
15
01
2020
revised:
13
04
2020
accepted:
13
04
2020
pubmed:
31
5
2020
medline:
31
5
2020
entrez:
31
5
2020
Statut:
ppublish
Résumé
We attempted to detect circulating tumor DNA (ctDNA), taking advantage of molecular barcode next-generation sequencing (MB-NGS), which can be more easily customized to detect a variety of mutations with a high sensitivity than PCR-based methods. Sequencing with a gene panel consisting of the 13 most frequently mutated genes in breast tumors from stage I or II patients revealed 95 somatic mutations in the 12 genes in 62% (62/100) of tumors. Then, plasma DNA from each patient (n = 62) before surgery was analyzed via MB-NGS customized to each somatic mutation, resulting in the detection of ctDNA in 16.1% (10/62) of patients. ctDNA was significantly associated with biologically aggressive phenotypes, including large tumor size (P = .004), positive lymph node (P = .009), high histological grade (P < .001), negative ER (P = .018), negative PR (P = .017), and positive HER2 (P = .046). Furthermore, distant disease-free survival was significantly worse in patients with ctDNA (n = 10) than those without ctDNA (n = 52) (P < .001). Our results demonstrate that MB-NGS personalized to each mutation can detect ctDNA with a high sensitivity in early breast cancer patients at diagnosis, and it seems to have a potential to serve as a clinically useful tumor marker for predicting their prognosis.
Identifiants
pubmed: 32473569
pii: S1936-5233(20)30019-X
doi: 10.1016/j.tranon.2020.100787
pmc: PMC7260577
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100787Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Références
Clin Cancer Res. 2018 Nov 15;24(22):5602-5609
pubmed: 29898991
Sci Transl Med. 2013 Oct 16;5(207):207ps14
pubmed: 24132635
Sci Transl Med. 2019 Aug 7;11(504):
pubmed: 31391323
Breast Cancer Res Treat. 2018 Feb;168(1):159-168
pubmed: 29177603
N Engl J Med. 2018 Nov 01;379(18):1754-1765
pubmed: 30380390
JAMA Oncol. 2019 Oct 1;5(10):1473-1478
pubmed: 31369045
Nucleic Acids Res. 2012 Dec;40(22):11189-201
pubmed: 23066108
Nat Rev Cancer. 2017 Apr;17(4):223-238
pubmed: 28233803
Nat Med. 2008 Sep;14(9):985-90
pubmed: 18670422
J Clin Epidemiol. 1996 Dec;49(12):1373-9
pubmed: 8970487
Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9530-5
pubmed: 21586637
EMBO Mol Med. 2015 Aug;7(8):1034-47
pubmed: 25987569
J Clin Oncol. 2014 Feb 20;32(6):579-86
pubmed: 24449238
Nature. 2012 Oct 4;490(7418):61-70
pubmed: 23000897
PLoS One. 2015 Oct 16;10(10):e0140712
pubmed: 26474073
Sci Transl Med. 2015 Nov 11;7(313):313ra182
pubmed: 26560360
Breast Cancer Res Treat. 2012 Feb;132(1):165-73
pubmed: 21594664
Genomics Proteomics Bioinformatics. 2017 Apr;15(2):59-72
pubmed: 28392479
Clin Cancer Res. 2019 Nov 1;25(21):6546-6553
pubmed: 31350313
Sci Transl Med. 2017 Aug 16;9(403):
pubmed: 28814544
Breast Cancer Res Treat. 2015 Apr;150(2):299-307
pubmed: 25736040
Clin Cancer Res. 2019 Jul 15;25(14):4255-4263
pubmed: 30992300
Clin Breast Cancer. 2017 Feb;17(1):61-69.e3
pubmed: 27395416
Oncology. 2012;83(5):273-82
pubmed: 22964822
Breast Cancer Res Treat. 2018 Jan;167(1):49-58
pubmed: 28905136
J Mol Diagn. 2018 Sep;20(5):686-702
pubmed: 29936259