We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Nucleosome footprinting in plasma cell-free DNA for the pre-surgical diagnosis of ovarian cancer.
- Authors
Vanderstichele, Adriaan; Busschaert, Pieter; Landolfo, Chiara; Olbrecht, Siel; Coosemans, An; Froyman, Wouter; Loverix, Liselore; Concin, Nicole; Braicu, Elena Ioana; Wimberger, Pauline; Van Nieuwenhuysen, Els; Han, Sileny N.; Van Gorp, Toon; Venken, Tom; Heremans, Ruben; Neven, Patrick; Bourne, Tom; Van Calster, Ben; Timmerman, Dirk; Lambrechts, Diether
- Abstract
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.
- Subjects
CELL-free DNA; CANCER diagnosis; ADNEXAL diseases; OVARIAN tumors; OVARIAN cancer; CHROMATIN; CIRCULATING tumor DNA
- Publication
NPJ Genomic Medicine, 2022, Vol 7, Issue 1, p1
- ISSN
2056-7944
- Publication type
Article
- DOI
10.1038/s41525-022-00300-5