Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 03 2023
01 03 2023
Historique:
received:
02
09
2022
accepted:
14
02
2023
entrez:
1
3
2023
pubmed:
2
3
2023
medline:
4
3
2023
Statut:
epublish
Résumé
Liquid biopsy has proven valuable in identifying individual genetic alterations; however, the ability of plasma ctDNA to capture complex tumor phenotypes with clinical value is unknown. To address this question, we have performed 0.5X shallow whole-genome sequencing in plasma from 459 patients with metastatic breast cancer, including 245 patients treated with endocrine therapy and a CDK4/6 inhibitor (ET + CDK4/6i) from 2 independent cohorts. We demonstrate that machine learning multi-gene signatures, obtained from ctDNA, identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to what is accomplished using direct tumor tissue DNA or RNA profiling. More importantly, 4 DNA-based subtypes, and a ctDNA-based genomic signature tracking retinoblastoma loss-of-heterozygosity, are significantly associated with poor response and survival outcome following ET + CDK4/6i, independently of plasma tumor fraction. Our approach opens opportunities for the discovery of additional multi-feature genomic predictors coming from ctDNA in breast cancer and other cancer-types.
Identifiants
pubmed: 36859416
doi: 10.1038/s41467-023-36801-9
pii: 10.1038/s41467-023-36801-9
pmc: PMC9977734
doi:
Substances chimiques
Circulating Tumor DNA
0
DNA, Neoplasm
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1157Informations de copyright
© 2023. The Author(s).
Références
Ann Oncol. 2018 Mar 1;29(3):640-645
pubmed: 29236940
Clin Cancer Res. 2020 Nov 15;26(22):5820-5829
pubmed: 32938620
BMC Cancer. 2019 May 30;19(1):521
pubmed: 31146704
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
NPJ Breast Cancer. 2021 Feb 3;7(1):8
pubmed: 33536433
Cancer Res. 2008 May 1;68(9):3108-14
pubmed: 18451135
Cancer Discov. 2018 Nov;8(11):1390-1403
pubmed: 30206110
BMC Med Genomics. 2011 Jan 09;4:3
pubmed: 21214954
Lancet Oncol. 2017 Apr;18(4):545-554
pubmed: 28238593
Nat Commun. 2018 Mar 1;9(1):896
pubmed: 29497091
Science. 1996 Dec 6;274(5293):1672-7
pubmed: 8939849
Sci Adv. 2021 Jul 7;7(28):
pubmed: 34233875
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Cell. 2014 Aug 14;158(4):929-944
pubmed: 25109877
Ann Oncol. 2023 Jan;34(1):111-120
pubmed: 36208697
Cancer Cell. 2018 Sep 10;34(3):427-438.e6
pubmed: 30205045
Nat Commun. 2017 Nov 6;8(1):1324
pubmed: 29109393
Nat Commun. 2019 Dec 11;10(1):5666
pubmed: 31827079
Lancet Oncol. 2020 Oct;21(10):1353-1365
pubmed: 32919526
Breast Cancer Res. 2009;11(5):R77
pubmed: 19874578
Nature. 2002 Jan 31;415(6871):530-6
pubmed: 11823860
Nature. 2012 Oct 4;490(7418):61-70
pubmed: 23000897
Cancers (Basel). 2021 Mar 30;13(7):
pubmed: 33808271
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
Nat Med. 2018 May;24(5):628-637
pubmed: 29713086
JAMA Oncol. 2016 Oct 01;2(10):1287-1294
pubmed: 27281556
Cancer Res. 2017 May 1;77(9):2213-2221
pubmed: 28249905
Ann Oncol. 2018 Sep 1;29(9):1895-1902
pubmed: 30137196
J Clin Oncol. 2020 Jan 1;38(1):1-10
pubmed: 31682550
Breast Cancer Res. 2008;10(4):R65
pubmed: 18662380
J Clin Oncol. 2009 Mar 10;27(8):1160-7
pubmed: 19204204
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
JCO Oncol Pract. 2021 Oct;17(10):594-604
pubmed: 34077236
JCO Precis Oncol. 2021 Sep 01;5:
pubmed: 34504990
Cancer Discov. 2021 Nov;11(11):2796-2811
pubmed: 34183353
J Clin Oncol. 2006 Apr 10;24(11):1656-64
pubmed: 16505416
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
pubmed: 9843981
J Clin Oncol. 2021 May 1;39(13):1458-1467
pubmed: 33769862
Nat Genet. 2016 Oct;48(10):1273-8
pubmed: 27571261
Nat Biotechnol. 2008 Mar;26(3):317-25
pubmed: 18278033
Clin Cancer Res. 2011 Apr 15;17(8):2591-601
pubmed: 21248301
BMC Cancer. 2006 Dec 06;6:276
pubmed: 17150101
Nat Rev Clin Oncol. 2016 Jul;13(7):417-30
pubmed: 27030077
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
pubmed: 11309499
Genome Biol. 2013 Nov 12;14(11):R125
pubmed: 24220145
Oncologist. 2019 Jul;24(7):893-900
pubmed: 30679318
Breast Cancer Res. 2008;10(5):R75
pubmed: 18782450
BMC Med. 2009 Mar 16;7:9
pubmed: 19291283
Clin Cancer Res. 2011 Mar 15;17(6):1591-602
pubmed: 21278246
Mol Oncol. 2011 Feb;5(1):5-23
pubmed: 21147047
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
JCO Precis Oncol. 2022 Oct;6:e2200261
pubmed: 36265119