Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
28 Apr 2022
28 Apr 2022
Historique:
received:
10
03
2021
accepted:
04
03
2022
entrez:
28
4
2022
pubmed:
29
4
2022
medline:
29
4
2022
Statut:
epublish
Résumé
Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions of cell types contributing to cfDNA. Based on cfDNA fragmentation patterns, the deviation in nucleosome footprints was quantified between diagnosed ovarian cancer patients and healthy individuals. Multinomial modeling was subsequently applied to capture these deviations in a per sample nucleosome footprint score. Validation was performed in 271 cfDNAs pre-surgically collected from women with an adnexal mass. We confirmed that nucleosome scores were elevated in invasive carcinoma patients, but not in patients with benign or borderline disease. Combining nucleosome scores with chromosomal instability scores assessed in the same cfDNA improved prediction of malignancy. Nucleosome scores were, however, more reliable to predict non-high-grade serous ovarian tumors, which are characterized by low chromosomal instability. These data highlight that compared to chromosomal instability, nucleosome footprinting provides a complementary and more generic read-out for pre-surgical diagnosis of invasive disease in women with adnexal masses.
Identifiants
pubmed: 35484288
doi: 10.1038/s41525-022-00300-5
pii: 10.1038/s41525-022-00300-5
pmc: PMC9050708
doi:
Types de publication
Journal Article
Langues
eng
Pagination
30Subventions
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G049312N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : G0B4716N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : 12F3114N
Organisme : Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)
ID : 18B2921N
Informations de copyright
© 2022. The Author(s).
Références
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16910-5
pubmed: 20837533
Nucleic Acids Res. 2018 Sep 6;46(15):e89
pubmed: 29897492
Nat Genet. 2013 Oct;45(10):1127-33
pubmed: 24071851
Gynecol Oncol Rep. 2017 Jan 06;19:57-58
pubmed: 28127584
Science. 2018 Oct 26;362(6413):
pubmed: 30361341
Nat Genet. 2016 Oct;48(10):1273-8
pubmed: 27571261
Nat Commun. 2018 Nov 29;9(1):5068
pubmed: 30498206
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nat Genet. 2017 Apr;49(4):635-642
pubmed: 28263317
Immunity. 2016 Dec 20;45(6):1327-1340
pubmed: 27939672
Clin Cancer Res. 2017 May 1;23(9):2223-2231
pubmed: 27852697
Prenat Diagn. 2016 Jul;36(7):614-21
pubmed: 26996738
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Sci Transl Med. 2010 Dec 8;2(61):61ra91
pubmed: 21148127
Prenat Diagn. 2013 Jul;33(7):662-6
pubmed: 23553731
Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1317-25
pubmed: 25646427
BMJ. 2014 Oct 15;349:g5920
pubmed: 25320247
Trends Genet. 2016 Jun;32(6):360-371
pubmed: 27129983
Nat Biotechnol. 2021 May;39(5):586-598
pubmed: 33432199
Gynecol Oncol. 1994 Dec;55(3 Pt 2):S42-6
pubmed: 7835810
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5503-12
pubmed: 26392541
Nature. 2019 Jun;570(7761):385-389
pubmed: 31142840
Gynecol Oncol. 2014 Dec;135(3):415-22
pubmed: 25281495
Genome Biol. 2017 Mar 24;18(1):53
pubmed: 28335812
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Nat Commun. 2020 Feb 26;11(1):1075
pubmed: 32103026
Cell. 2016 Jan 14;164(1-2):57-68
pubmed: 26771485
Cancer Cell. 2019 Oct 14;36(4):350-368
pubmed: 31614115